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Sample records for spontaneously hypertensive stroke

  1. Interleukin-1β Accelerates the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

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    Tsuyoshi Chiba

    2012-01-01

    Full Text Available High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP. At 4 weeks of age (before stroke onset, the plasma level of IL-1β was significantly higher in SHRSP (153.0±49.7 pg/ml than in Wistar Kyoto rats (WKY (7.7±3.4 pg/ml, P<0.001 versus SHRSP or spontaneously hypertensive rats (SHR (28.0±9.1 pg/ml, P<0.001 versus SHRSP (n=6 per strain. Stimulated IL-1β signal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1, which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β (2 μg/day using an osmotic pump slightly increased the incidence of stroke in SHR (P=0.046 and significantly accelerated the onset of stroke in SHRSP (P=0.006 compared to each control (n=10 per group. These results suggest that a stimulated IL-1β signal might be a cause of stroke onset when concomitant with severe hypertension.

  2. Effects of aniracetam on impaired sleep patterns in stroke-prone spontaneously hypertensive rats.

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    Kimura, M; Okano, S; Inoué, S

    2000-06-01

    The aim of the present study was to determine the pattern of sleep disturbances and the effects on sleep of aniracetam, a cognitive enhancer, in stroke-prone spontaneously hypertensive rats (SHRSP). Compared with normotensive control rats, SHRSP exhibited an impaired sleep pattern characterized by suppressed diurnal rapid eye movement (REM) sleep and excessive nocturnal non-REM sleep. At a dose of 30 mg/kg per day p.o., aniracetam increased REM sleep in the light period after administration for 5 consecutive days. Consequently, suppressed REM sleep in SHRSP was restored by repeated treatment with aniracetam. Aniracetam could be useful in improving REM sleep impairment associated with vascular dementia.

  3. Aniracetam enhances glutamatergic transmission in the prefrontal cortex of stroke-prone spontaneously hypertensive rats.

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    Togashi, Hiroko; Nakamura, Kazuo; Matsumoto, Machiko; Ueno, Ken-ichi; Ohashi, Satoshi; Saito, Hideya; Yoshioka, Mitsuhiro

    2002-03-08

    The effects of aniracetam, a cognition enhancer, on extracellular levels of glutamate (Glu), gamma-aminobutyric acid (GABA) and nitric oxide metabolites (NOx) were examined in the prefrontal cortex (PFC) and the basolateral amygdala (AMG) in stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal release of Glu, was lower in the AMG of SHRSP than in normotensive Wistar Kyoto rats, whereas no difference in GABA and NOx was noted. Aniracetam (100 mg/kg, p.o.) significantly increased the area under the curve of Glu levels in the PFC, but not in the AMG, of SHRSP. Aniracetam failed to exert any remarkable effects on GABA or NOx levels in either brain region. Our findings suggest that aniracetam enhances cortical glutamatergic release, which may be the mechanism involved in the ameliorating effects of aniracetam on various neuronal dysfunctions.

  4. Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat

    NARCIS (Netherlands)

    Sampson, Amanda K.; Mohammed, Dashti; Beattie, Wendy; Graham, Delyth; Kenyon, Christopher J.; Al-Dujaili, Emad A. S.; Guryev, Victor; Mcbride, Martin W.; Dominiczak, Anna F.

    2014-01-01

    Background: The genetic contribution to salt-sensitivity in hypertension remains unclear. We have previously identified a quantitative trait locus on chromosome 2 in stroke-prone spontaneously hypertensive rats (SHRSPs) responsible for an increase in SBP in response to a salt challenge. This

  5. Superoxide dismutase mimetic, tempol, aggravates renal injury in advanced-stage stroke-prone spontaneously hypertensive rats.

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    Sugama, Ikuko; Kohagura, Kentaro; Yamazato, Masanobu; Nakamura, Takuto; Shinzato, Tomoko; Ohya, Yusuke

    2014-03-01

    The aim of this study was to determine whether antioxidant therapy could relieve hypertension and retard the progression of renal damage in advanced-stage hypertensive rats. Twenty-four-week-old spontaneously hypertensive stroke-prone rats were treated for 8 weeks with the superoxide dismutase mimetic tempol, low-dose or high-dose candesartan (an angiotensin receptor blocker), or hydralazine, and blood pressure and renal damage were compared. Elevated blood pressure and renal damage with heterogeneity were present after 8 weeks, with greater glomerulosclerosis in the juxtamedullary glomeruli than in the superficial glomeruli. Although both tempol and candesartan effectively reduced reactive oxygen species production in the kidney, tempol did not decrease blood pressure and exacerbated urine protein and histological damage, such as glomerulosclerosis and interstitial fibrosis, particularly in juxtamedullary nephrons (tempol vs. untreated: glomerulosclerosis index, 2.0 vs. 1.5, Ptempol-treated rats, suggesting that changes in glomerular hemodynamics may be responsible for the exacerbation of glomerulosclerosis. Both candesartan- and hydralazine-treated rats had glomeruli that were slightly decreased in size. These results suggest that single-antioxidant therapy starting at an advanced-stage may be ineffective for hypertension and rather exacerbate renal damage in nonsalt loaded SHRSP. Furthermore, lowering blood pressure and inhibiting the renin-angiotensin system could be critical for slowing the progression of hypertensive renal damage at an advanced stage.

  6. Normal values of quantitative T2′ in a spontaneously hypertensive stroke prone rat stem at 3 T

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    Jensen-Kondering, U.; Böhm, R.; Höcker, J.; Ruhe, R.; Brdon, J.; Ulmer, S.; Herdegen, T.; Jansen, O.

    2012-01-01

    Introduction: Regarding therapy and prognosis of acute ischemic stroke the identification of ischemic penumbra is pivotal. A promising candidate is BOLD-imaging using qT2′-maps. For valid interpretation of experimental studies in animals normal values for qT2′ are needed. Normal values in humans at 1.5 T already exist. Normal values for cortical and subcortical structures in a spontaneously hypertensive stroke prone rat stem (SHR-SP) at a fieldstrength of 3 T are reported. Materials and methods: 39 (20 males and 19 females) spontaneously hypertensive stroke prone (SHRSP) rats were examined in a 3 T scanner using a dedicated small animal coil. Mean weight was 144.1 ± 8.2 g and mean age was 60.2 ± 2.7 days. For the calculation of qT2′ multiple echo T2w and T2*w images were acquired. ROIs were placed into deep and cortical grey matter in five different brain regions to obtain values for qT2′, qT2 and qT2*. Results: Mean qT2′ for cortical grey matter was 74.76 ± 33.27 ms and 67.73 ± 17.86 ms for deep grey matter. The 99% confidence interval for cortical grey matter was 69.91–79.61 ms. For qT2 it was 79.02 ± 2.9 ms and 70.45 ± 1.89 ms, respectively. For qT2* it was 34.65 ± 5.25 ms and 31.9 ± 2.99 ms. Conclusion: The values for qT2′ presented here can serve as reference values for further studies examining the ischemic penumbra in a rat model.

  7. Effect of chlorella and its fractions on blood pressure, cerebral stroke lesions, and life-span in stroke-prone spontaneously hypertensive rats.

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    Sansawa, Hiroshi; Takahashi, Masatoshi; Tsuchikura, Satoru; Endo, Hiroshi

    2006-12-01

    Effects of Chlorella regularis (dried cell powder)--cultured axenically under heterotrophic conditions, and provided as a dietary supplement--and its fractions on the blood pressure, cerebral stroke lesions, and life-span of stroke-prone spontaneously hypertensive rats (SHRSP/Izm) were investigated. When SHRSP were fed on diets with supplemented Chlorella to a commercial diet (Funabashi SP), elevation of blood pressure was significantly lower in the Chlorella groups than in the control group. At 21 wk of feeding, serum total cholesterol was significantly lower in the Chlorella groups than in the control group. Histopathological examination revealed cerebral vascular accidents in the brains of the control group, but those of Chlorella groups showed apparently low incidence compared to the control group. The average life-span of the Chlorella groups were significantly longer than that of the control group (p vascular function of rats.

  8. Involvement of arterial baroreflex and nicotinic acetylcholine receptor α7 subunit pathway in the protection of metformin against stroke in stroke-prone spontaneously hypertensive rats.

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    Guo, Jin-Min; Zhang, Li; Niu, Xue-Cai; Shu, He; Wang, Lei; Su, Ding-Feng; Zhang, Ying; Liu, Ai-Jun; Zhu, De-Qiu; Xu, Jian-Jiang

    2017-03-05

    Stroke is a leading cause of mortality and disability worldwide. There is growing evidence that metformin (Met) has potent neuroprotective effects; however, its mechanisms remain unclear. We examined the role of the arterial baroreflex and cholinergic-α7 nicotinic acetylcholine receptor (α7nAChR) anti-inflammory pathway in the beneficial effects of Met against stroke. Stroke-prone spontaneously hypertensive rats (SHRSP) were used to observe stroke development indicated by lifespan of SHRSP and the ischemic injury induced by permanent middle cerebral artery occlusion (MCAO). Sinoaortic denervation was used to inactivate the arterial baroreflex. MCAO were also performed in α7nAChR knockout (KO) mice. Briefly, Met increased the life span of SHRSP and reduced the infarct area induced by MCAO. Met also improved the function of arterial baroreflex. The beneficial effects of Met on stroke were markedly attenuated by blunting the arterial baroreflex. Met up-regulated the expression of vesicular acetylcholine transporter (VAChT) and α7nAChR, down-regulated the level of pro-inflammtory cytokines in serum and peri-infarct of ischemic brain. Arterial baroreflex dysfunction decreased the expression of VAchT and α7nAChR, showed upward tendency in the level of pro-inflammtory cytokines. Most importantly, arterial baroreflex dysfunction nearly abolished such effect of Met on cholinergic signaling. In addition, the α7nAChR KO mice also had significantly worse ischemic damage induced by MCAO, and neuroprotection of Met disappeared in α7nAChR KO mice. In conclusion, Met improved the arterial baroreflex function, and then enhancing cholinergic anti-inflammatory pathway in an α7nAChR-dependent manner, thereby effectively prevent ischemic induced brain injury and delayed stroke onset in SHRSP. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Vasodilator effects of fasudil, a Rho-kinase inhibitor, on retinal arterioles in stroke-prone spontaneously hypertensive rats.

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    Okamura, Nami; Saito, Maki; Mori, Asami; Sakamoto, Kenji; Kametaka, Sokichi; Nakahara, Tsutomu; Ishii, Kunio

    2007-06-01

    The aim of this study was to examine the vasodilator effect of fasudil, a Rho-kinase inhibitor, on retinal arterioles in stroke-prone spontaneously hypertensive rats (SHRSPs) and in age-matched normotensive Wistar-Kyoto rats (WKYs). Rats (12-14 weeks-old) were anesthetized with thiobutabarbital (120 mg/kg, intraperitoneal). Fundus images were captured with a digital camera that was equipped with a special objective lens. The vasodilator responses of retinal arterioles were assessed by measuring changes in the diameters of the vessels. The baseline diameter of the retinal arteriole was significantly smaller in SHRSPs than in WKYs. Fasudil (50-200 microg/kg/min, intravenous) dose-dependently increased the diameter of the retinal arteriole and decreased the systemic blood pressure in both groups. The vasodilator effect of fasudil on the retinal arteriole in SHRSPs was greater than in WKYs. These results suggest that fasudil has beneficial effects on retinal vascular complications associated with chronic hypertension.

  10. Decreased cerebral metabolism in stroke-prone spontaneously hypertensive rats (SHRSP) with stroke and its possible improvement by Solcoseryl.

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    Yamasaki, Y; Yamamoto, Y; Senga, Y; Isogai, M; Shimizu, H; Yamori, Y

    1991-01-01

    Local cerebral glucose utilization (LCGU) was decreased in SHRSP with stroke compared with normotensive Wistar rats. The decrement of LCGU was less in Solcoseryl-treated SHRSP with stroke than that in saline-treated SHRSP with stroke and these brain areas where LCGU was less damaged, in Solcoseryl-treated SHRSP were consistent with the important functioning sites of emotion, motor movement and memory. The result suggests that Solcoseryl may be useful for metabolic improvement of the brain damage after stroke.

  11. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.

    2013-01-01

    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  12. SELECTIVE CHLORIDE LOADING IS PRESSOR IN THE STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RAT DESPITE HYDROCHLOROTHIAZIDE-INDUCED NATRIURESIS

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    Schmidlin, Olga; Tanaka, Masae; Sebastian, Anthony; Morris, R. Curtis

    2010-01-01

    Objective To test the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the pressor effect of selective dietary chloride loading depends on a positive external sodium balance. Methods In 43 male SHRSP fed a Japanese style diet containing a low normal amount of NaCl (0.4%) we compared the effects on telemetrically measured systolic blood pressure (SBP) of hydrochlorothiazide, 25 mg/kg per day, alone (“TZ”, n=11); hydrochlorothiazide combined with either KCl (“KCLTZ”, 2%K, n=10) or KHCO3 (“KBCTZ”, 2%K, n=11) and no hydrochlorothiazide (“CTL”, n=11) over a 10-week period starting at 10 weeks of age. Results With either TZ or KBCTZ, SBP did not increase above baseline values. However, KCLTZ induced a sustained increase in SBP of 17 mmHg (phydrochlorothiazide (CTL), 38 mmHg (phydrochlorothiazide, but did not differ between KCLTZ and KBCTZ. Changes in SBP occurring on the 2nd day after treatment assignment predicted final changes. Conclusions These results demonstrate that in the SHRSP, dietary KCl loading can induce a pressor effect despite concomitant hydrochlorothiazide-induced natriuresis that elicits a negative external sodium balance. The results provide evidence that in the SHRSP the pressor effect of selective chloride loading does not depend on a positive external sodium balance, but rather on a mechanism actuated by chloride per se. PMID:19851120

  13. Hypertension-Induced Vascular Remodeling Contributes to Reduced Cerebral Perfusion and the Development of Spontaneous Stroke in Aged SHRSP Rats

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    2010-01-01

    additional. thrombosis (Figure 4, top row, asterisks) and diapedesis of blood. Affected vessels were 100 to 250 J.lm in diameter (average 150 J.lm (40...hypertensive rats. Stroke 29:1671-7; discussion 1677-1678 Blezer EL, Schurink M, Nicolay K, Bar PR, Jansen GH, Koomans HA, Joles JA (1998b) Proteinuria

  14. Protective effects of D-Limonene against transient cerebral ischemia in stroke-prone spontaneously hypertensive rats.

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    Wang, Xifeng; Li, Gang; Shen, Wei

    2018-01-01

    Stroke is a leading cause of disability and death world-wide and there is currently a lack of effective treatments for acute stroke. D-Limonene is a common natural monocyclic monoterpene possessing various activities. The present study aimed to evaluate the therapeutic efficacy of D-limonene against ischemia-associated cerebral injury in hypertensive SHRsp rats. Although systolic blood pressure was not altered by ischemia, D-Limonene decreased the systolic blood pressure of SHRsp rats following stroke. Induction of stroke resulted in increased escape latency time, decreased time spent in the target quadrant in the probe trial, decreased capacity to distinguish between familiar objects and novel objects, and increased sensory neglect in the SHRsp rat, however these symptoms were significantly inhibited by D-limonene. D-limonene also decreased the cerebral infarct size in the SHRsp rats following stroke. D-Limonene markedly decreased the mRNA expression of interleukin-1β, monocyte chemoattractant protein-1 and cyclooxygenase-2 in SHRsp rats following stroke. The mRNA expression of vascular endothelial growth factor in the brain of SHRsp rats following stroke was significantly increased by D-Limonene. D-Limonene increased the activities of superoxide dismutase and catalase, decreased the malondialdehyde level, increased glutathione content and reduced the DHE-staining in SHRsp rats following stroke. Overall, inhibition of cerebral inflammation, vascular remodeling and antioxidant activities of D-Limonene may be involved in the protective effects against ischemia-induced damage in SHRsp rats. The present study identified D-Limonene as a potential therapeutic candidate for treatment of stroke-associated cerebral and vascular damage under conditions of hypertension.

  15. Influence of sources of dietary oils on the life span of stroke-prone spontaneously hypertensive rats.

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    Ratnayake, W M; Plouffe, L; Hollywood, R; L'Abbé, M R; Hidiroglou, N; Sarwar, G; Mueller, R

    2000-04-01

    In recent studies, the life span of stroke-prone spontaneously hypertensive (SHRSP) rats was altered by a variety of dietary fats. It was relatively shorter in rats fed canola oil as the sole source of fat. The present study was performed to find out whether the fatty acid profile and the high content of sulfur compounds in canola oil could modulate the life span of SHRSP rats. SHRSP rats (47 d old, n = 23/group) were matched by body weight and systolic blood pressure and fed semipurified diets containing 10% canola oil, high-palmitic canola oil, low-sulfur canola oil, soybean oil, high-oleic safflower oil, a fat blend that mimicked the fatty acid composition of canola oil, or a fat blend high in saturated fatty acids. A 1% sodium chloride solution was used as drinking water to induce hypertension. After consuming the diets for 37 d, five rats from each dietary group were killed for collection of blood and tissue samples for biochemical analysis. The 18 remaining animals from each group were used for determining their life span. The mean survival time of SHRSP rats fed canola oil (87.4+/-4.0 d) was not significantly different (P > 0.05) from those fed low-sulfur canola oil (89.7+/-8.5 d), suggesting that content of sulfur in canola oil has no effect on the life span of SHRSP rats. The SHRSP rats fed the noncanola oil-based diets lived longer (mean survival time difference was 6-13 d, P < 0.05) than those fed canola and low-sulfur canola oils. No marked differences in the survival times were observed among the noncanola oil-based groups. The fatty acid composition of the dietary oils and of red blood cells and liver of SHRSP rats killed after 37 d of treatment showed no relationship with the survival times. These results suggest that the fatty acid profile of vegetable oils plays no important role on the life span of SHRSP rat. However, phytosterols in the dietary oils and in liver and brain were inversely correlated with the mean survival times,indicating that the

  16. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats.

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    Ardiansyah; Ohsaki, Yusuke; Shirakawa, Hitoshi; Koseki, Takuya; Komai, Michio

    2008-04-23

    We studied the effects of a single oral administration of ferulic acid (FA) on the blood pressure (BP) and lipid profile in stroke-prone spontaneously hypertensive rats (SHRSP). Male 12-week-old SHRSP were administered FA (9.5 mg/kg of body weight) and distilled water as the control (C) (1 mL) via a gastric tube. The hypotensive effect of FA was observed at the lowest value after 2 h administration. A decrease in the angiotensin-1-converting enzyme (ACE) activity in the plasma corresponded well with the reduction of BP. Plasma total cholesterol and triglyceride levels were lower after 2 h administration. The mRNA expression of genes involved in lipid and drug metabolism was downregulated in the FA group. These results suggest that oral administration of FA appears beneficial in improving hypertension and hyperlipidemia.

  17. Effect of tempol and tempol plus catalase on intra-renal haemodynamics in spontaneously hypertensive stroke-prone (SHSP) and Wistar rats.

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    Ahmeda, Ahmad F; Rae, Mark G; Al Otaibi, Mohammed F; Anweigi, Lamyia M; Johns, Edward J

    2017-05-01

    Vasoconstriction within the renal medulla contributes to the development of hypertension. This study investigated the role of reactive oxygen species (ROS) in regulating renal medullary and cortical blood perfusion (MBP and CBP respectively) in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar rats. CBP and MBP were measured using a laser-Doppler flow meter before and after intra-renal infusion of tempol, the superoxide dismutase (SOD) mimetic or tempol plus catalase, the hydrogen peroxide-degrading enzyme. Tempol infusion significantly elevated blood perfusion within the renal medulla (MBP) in both SHRSP (by 43 ± 7%, P catalase and tempol were co-infused, MBP was again significantly increased in SHRSP (by 57 ± 6%, P < 0.001) and Wistar rats (by 33 ± 6%, P < 0.001), with a significantly greater increase in perfusion being induced in the SHRSP relative to the Wistar rats (P < 0.01). Notably, this increase was significantly greater than in those animals infused with tempol alone (P < 0.01). These results suggest that ROS plays a proportionally greater role in reducing renal vascular compliance, particularly within the renal medulla, in normotensive and hypertensive animals, with effects being greater in the hypertensive animals. This supports the hypothesis that SHRSP renal vasculature might be subjected to elevated level of oxidative stress relative to normotensive animals.

  18. Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats.

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    Cipolla, Marilyn J; Linfante, Italo; Abuchowski, Abe; Jubin, Ronald; Chan, Siu-Lung

    2018-05-01

    Similar to patients with chronic hypertension, spontaneously hypertensive rats (SHR) develop fast core progression during middle cerebral artery occlusion (MCAO) resulting in large final infarct volumes. We investigated the effect of Sanguinate™ (SG), a PEGylated carboxyhemoglobin (COHb) gas transfer agent, on changes in collateral and reperfusion cerebral blood flow and brain injury in SHR during 2 h of MCAO. SG (8 mL/kg) or vehicle ( n = 6-8/group) was infused i.v. after 30 or 90 min of ischemia with 2 h reperfusion. Multi-site laser Doppler probes simultaneously measured changes in core MCA and collateral flow during ischemia and reperfusion using a validated method. Brain injury was measured using TTC. Animals were anesthetized with choral hydrate. Collateral flow changed little in vehicle-treated SHR during ischemia (-8 ± 9% vs. prior to infusion) whereas flow increased in SG-treated animals (29 ± 10%; p collateral flow in SHR during MCAO is consistent with small penumbra and large infarction. The ability to increase collateral flow in SHR with SG suggests that this compound may be useful as an adjunct to endovascular therapy and extend the time window for treatment.

  19. Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under high-salt/low-potassium diet.

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    Di Castro, Sara; Scarpino, Stefania; Marchitti, Simona; Bianchi, Franca; Stanzione, Rosita; Cotugno, Maria; Sironi, Luigi; Gelosa, Paolo; Duranti, Enrico; Ruco, Luigi; Volpe, Massimo; Rubattu, Speranza

    2013-02-01

    The stroke-prone spontaneously hypertensive rat (SHRsp) represents an animal model of increased susceptibility to high-salt diet-induced cerebral and renal vascular injuries. High blood pressure and genetic factors are viewed as major contributing factors. In high-salt-loaded SHRsp and stroke-resistant SHR animals, we determined blood pressure levels, degree of kidney lesions, renal uncoupling protein 2 (UCP2) gene and protein expression levels along with rattus norvegicus (rno)-microRNA (miR) 24 and 34a gene expression, nuclear factor-κB protein levels, and oxidative stress. In vitro, UCP2 gene silencing was performed in renal mesangial cells. We found more severe degree of renal damage in SHRsp at the end of 4-week high-salt dietary treatment as compared with stroke-resistant SHR, despite comparable blood pressure levels, along with increased rate of inflammation and oxidative stress. Kidney UCP2 gene and protein expression levels were significantly downregulated under high-salt diet in SHRsp, but not in stroke-resistant SHR. Differential UCP2 regulation was paralleled by differential expression of kidney rno-miR 24 and 34a, known to target UCP2 gene, in the 2 strains. UCP2 gene silencing in renal mesangial cells led to increased rate of reactive oxygen species generation, increased inflammation and apoptosis, reduced cell vitality, and increased necrosis. In conclusion, high-salt diet downregulates the antioxidant UCP2-dependent mechanism in kidneys of SHRsp, but not of stroke-resistant SHR. A parallel differential kidney miR regulation under high-salt diet in the 2 strains may contribute to the differential UCP2 modulation. UCP2 is a critical protein to prevent oxidative stress damage in renal mesangial cells in vitro.

  20. Arginine vasopressin regulated ASCT1 expression in astrocytes from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats.

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    Yamagata, K; Yamamoto, M; Kawakami, K; Ohara, H; Nabika, T

    2014-05-16

    In stroke-prone spontaneously hypertensive rats (SHRSP/Izm), ischemia induces swelling of astrocytes, a process that subsequently leads to neuronal death. Following ischemic insult, arginine vasopressin (AVP) can induce edema and l-serine released by astrocytes supports the survival of neuronal cells. The purpose of this study was to examine whether AVP contributed to the regulation of l-serine production following ischemic stroke. Here, we used cultured astrocytes from SHRSP/Izm rats and Wistar Kyoto rats (WKY/Izm) to examine whether AVP changed the production of l-serine and/or altered gene expression levels of the neural amino acid transporter (Slc1a4), 3-phosphoglycerate dehydrogenase (Phgdh) and serine racemase (SRR). Furthermore, using astrocytes from the congenic rat SHRpch1_18 strain having quantitative trait loci (QTL) of stroke, we examined expression of those genes under conditions of hypoxia and reoxygenation (H/R). The expression levels of ASCT1 protein, the genes described above and l-serine levels were determined by Western blotting (WB), RT-PCR, real-time quantitative RT-PCR and HPLC. AVP increased the production of l-serine and the expression of Slc1a4 in WKY/Izm and SHRSP/Izm astrocytes. The production of l-serine and the expression of Slc1a4 were lower in SHRSP/Izm than in WKY/Izm cells. This difference was not seen with Phgdh. In the SHRpch1_18 strain, the expression of Slc1a4 and Phgdh significantly decreased after H/R. AVP-mediated enhanced expression of ASCT1 was blocked by the addition of bumetanide. These results suggest that the AVP-mediated attenuated expression of ASCT1 in astrocytes is associated with reduced l-serine production in SHRSP/Izm astrocytes. We hypothesize that reduction of gene expression by AVP might be related to the induction of stroke in the SHRpch1_18 rat strain. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Histomorphometric, biochemical and ultrastructural changes in the aorta of salt-loaded stroke-prone spontaneously hypertensive rats fed a Japanese-style diet.

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    Baccarani Contri, M; Taparelli, F; Miselli, M; Bacchelli, B; Biagini, G

    2003-02-01

    It is demonstrated that dietary habits play a role in cardiovascular diseases. In stroke-prone spontaneously hypertensive rats (SHRsp), concomitant salt loading and a Japanese-style diet greatly accelerate hypertension and the appearance of cerebrovascular lesions by directly damaging arterial vessels. A number of studies have characterised medium and small vessel lesions in SHRsp, but little attention has been paid to the changes in the wall structure of large arteries induced by exposure to a salt-enriched diet. The aim of this study was to investigate the effects of a Japanese-style diet and salt loading on the thoracic aorta. Two-month-old SHRsp were kept on a Japanese-style diet with 1% sodium chloride solution replacing tap water. Two months later, they were sacrificed and compared with age-matched or two-month-old control SHRsp kept on a standard diet and tap water in terms of the histomorphometry, ultrastructure and biochemical composition of the thoracic aorta. The vessel was consistently thicker in the four-month-old SHRsp (+20%, p vs two-month-old rats) regardless of diet. The salt-loaded SHRsp showed a significant reduction in elastic fibre density (-20%, p vs two-month-old rats) and an increase in the other matrix components (%), whereas the four-month-old controls showed preserved elastic fibres and a significant increase in the other matrix components (+65%, p vs two-month-old rats). There was a considerable increase in the amounts of 4-OH-proline (+147%), 5-OH-lysine (+174%) and desmosines (+360%) in the four-month-old controls vs their two-month-old counterparts (p two months of treatment.

  2. Identification of Stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat.

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    Mohammed Zubaerul Ferdaus

    Full Text Available The stroke-prone spontaneously hypertensive rat (SHRSP is known to have exaggerated sympathetic nerve activity to various types of stress, which might contribute to the pathogenesis of severe hypertension and stroke observed in this strain. Previously, by using a congenic strain (called SPwch1.72 constructed between SHRSP and the normotensive Wistar-Kyoto rat (WKY, we showed that a 1.8-Mbp fragment on chromosome 1 (Chr1 of SHRSP harbored the responsible gene(s for the exaggerated sympathetic response to stress. To further narrow down the candidate region, in this study, another congenic strain (SPwch1.71 harboring a smaller fragment on Chr1 including two functional candidate genes, Phox2a and Ship2, was generated. Sympathetic response to cold and restraint stress was compared among SHRSP, SPwch1.71, SPwch1.72 and WKY by three different methods (urinary norepinephrine excretion, blood pressure measurement by the telemetry system and the power spectral analysis on heart rate variability. The results indicated that the response in SPwch1.71 did not significantly differ from that in SHRSP, excluding Phox2a and Ship2 from the candidate genes. As the stress response in SPwch1.72 was significantly less than that in SHRSP, it was concluded that the 1.2-Mbp congenic region covered by SPwch1.72 (and not by SPwch1.71 was responsible for the sympathetic stress response. The sequence analysis of 12 potential candidate genes in this region in WKY/Izm and SHRSP/Izm identified a nonsense mutation in the stromal interaction molecule 1 (Stim1 gene of SHRSP/Izm which was shared among 4 substrains of SHRSP. A western blot analysis confirmed a truncated form of STIM1 in SHRSP/Izm. In addition, the analysis revealed that the protein level of STIM1 in the brainstem of SHRSP/Izm was significantly lower when compared with WKY/Izm. Our results suggested that Stim1 is a strong candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP.

  3. The lack of age-pigments and the alterations in intracellular monovalent electrolytes in spontaneously hypertensive, stroke-prone (SHRsp) rats as revealed by electron microscopy and X-ray microanalysis

    International Nuclear Information System (INIS)

    Nagy, I.; Nagy, V.; Casoli, T.; Lustyik, G.

    1989-01-01

    Male, spontaneously hypertensive, stroke-prone (SHRsp) rats established by Okamoto et al. were studied. About 80% of the males of this strain have a particularly short life span (33-41 weeks); they display a considerable hypertension (above 220 mmHg) and a tendency for plurifocal brain strokes. Hypertension and strokes can be provoked in an accelerated and synchronized fashion by supplementing 1% NaCl into their drinking water. Symptoms of the appearance of brain strokes can be judged from characteristic signs of motor disorders, and can be established also by pathohistology. Since hypertension and arteriosclerosis are frequently involved in aging, the question we intended to answer was whether these animals may represent a model of the normal aging process or not. Two approaches are described: (1) Accumulation of lipofuscin granules in their brain, liver and myocardium was followed by transmission electron microscopy before and after the appearance of strokes. It has been established that these tissues do not show any typical accumulation of lipofuscin granules, although submicroscopic signs of an enhanced damage of cell organelles (especially of mitochondria in liver and brain cells, but not in myocardium) were encountered. (2) The intracellular monovalent composition in the brain and liver was measured by using bulk-specimen X-ray microanalysis. The intracellular Na-content (mEq/kg water) was significantly higher (170-200%) in both the brain and liver cells, whereas the K-content increased only moderately (118-130%). The results suggest that although the SHRsp rats do not represent a direct model for the normal aging process from the point of view of lipofuscin accumulation, the shifts of the monovalent electrolyte contents in the brain and liver cells observed already in the youngest ages, are similar to those observed in aged normal rats

  4. Surgical management of spontaneous hypertensive brainstem hemorrhage

    Directory of Open Access Journals (Sweden)

    Bal Krishna Shrestha

    2015-09-01

    Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.

  5. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However...

  6. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de

    1987-01-01

    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  7. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1......, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion...

  8. Management of hypertension in the setting of acute ischemic stroke.

    Science.gov (United States)

    Heitsch, Laura; Jauch, Edward C

    2007-12-01

    The optimal management of blood pressure in the first 24 hours of ischemic stroke remains a controversial topic. Most patients are hypertensive at presentation and subsequently experience a spontaneous decline in blood pressure. Decreasing penumbral blood flow and exacerbating vasogenic edema are significant concerns in whether to treat blood pressure elevations. Although an initially elevated blood pressure has been associated with poor outcome, attempts to acutely lower blood pressure are also associated with worsened outcomes. Thus, the current approach in acute ischemic stroke is permissive hypertension, in which antihypertensive treatment is warranted in patients with systolic blood pressure greater than 220 mm Hg, receiving thrombolytic therapy, or with concomitant medical issues. The use of predictable and titratable medications that judiciously reduce (approximately 10% to 15%) the initial presenting mean arterial pressure is recommended in these situations. Future study must define optimal blood pressure goals, likely on an individual basis.

  9. Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension

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    Rodrigo Vanerson Passos Neves

    2016-01-01

    Full Text Available Abstract Background: Resistance training (RT has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH. Objective: This study examined the effects of two RT protocols (vertical ladder climbing, performed at different overloads of maximal weight carried (MWC, on blood pressure (BP and muscle strength of spontaneously hypertensive rats (SHR with SH. Methods: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBPENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP were divided into 4 groups: sedentary (SED-WKY and SHR (SED-SHR; RT1-SHR training relative to body weight (~40% of MWC; and RT2-SHR training relative to MWC test (~70% of MWC. Systolic BP and heart rate (HR were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05, whereas SBP of the SED-SHR group increased by 19 mmHg (p 0.05. Conclusions: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.

  10. [Echocardiographic study of left ventricular geometry in spontaneously hypertensive rats].

    Science.gov (United States)

    Escudero, Eduardo M; Pinilla, Oscar A; Carranza, Verónica B

    2009-01-01

    The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters. Normal LV was defined considering the mean plus 2 SD of LVMI and RWT in W. Patterns of abnormal LV geometry were: LV concentric remodeling, LVMI 0.71; eccentric, left ventricular hypertrophy (LVH), LVMI > 2.06 mg/g - RWT 2.06 mg/g - RWT > 0.71. Systolic blood pressure (SBP) and cardiac output (CO) were used to obtain total peripheral resistance (TPR). twelve % of SHR had normal LV geometry; 18% LV concentric remodeling; 33% concentric LVH and 37% eccentric LVH. LV concentric remodeling showed the smallest CO and highest TPR of any group. Eccentric LVH presented similar SBP as the other SHR groups and high CO with lower TPR. Our findings in SHR exhibit different patterns of LV geometry like in humans. These results strengthen the similarities between SHR and human essential hypertension.

  11. Does Diagnosis of Hypertension Prevent Stroke? A Preliminary ...

    African Journals Online (AJOL)

    Introduction: The present study was designed to determine the relative frequency of previously diagnosed and undiagnosed hypertension in first stroke in order to evaluate if previous diagnosis of hypertension can prevent stroke. Patients and Methods: One hundred and twenty nine first stroke patients presenting at the ...

  12. Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

    DEFF Research Database (Denmark)

    Thomsen, Barbara Blicher; Gredal, Hanne; Wirenfeldt, Martin

    2017-01-01

    Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human....../macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies....... stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7 years and 8 months old female neutered Rottweiler dog suffered...

  13. Pathogenesis of hypercalciuria in spontaneously hypertensive rats.

    Science.gov (United States)

    Hsu, C H; Chen, P S; Smith, D E; Yang, C S

    1986-01-01

    The etiology of hypercalciuria remains unknown in spontaneously hypertensive rats (SHR). In order to differentiate absorptive versus renal hypercalciuria, serial measurements of urinary calcium (UCaV) excretion were made weekly under fasting (3-hour urine collection) and after oral administration of CaCl2 (50 mg/100 g; 4-hour urine collection) from age 8 to 14 weeks in SHR (n = 14) and normotensive Wistar Kyoto rats (WKY; n = 14). Fasting UCaV was significantly greater in WKY than in SHR throughout the periods of observation. In contrast, after oral Ca loading UCaV was greater in SHR after 13 weeks of age (13 weeks: SHR UCaV = 954 micrograms/mg creatinine, WKY UCaV = 541 p less than 0.01; 14 weeks: SHR UCaV = 988 micrograms/mg creatinine, WKY UCaV = 534, p less than 0.01). Fasting urinary cyclic adenosine monophosphate (AMP) excretion was not different between WKY and SHR. However, cyclic AMP excretion of SHR, but not WKY, was decreased after calcium loading when compared to the fasting values. The cyclic AMP was also significantly lower in SHR than in WKY rats after calcium loading. Calcium handling by the kidney was not different between SHR and WKY with or without parathyroidectomy. Calcium disposition kinetic studies were performed on these animals at age 15 and 16 weeks. No significant difference of intravenous 45Ca was observed between WKY (n = 6) and SHR (n = 6) in total plasma clearance, nonrenal clearance, biologic half-life, and elimination rate constant from the central compartment. However, the WKY had a significantly greater renal clearance of 45Ca than the SHR (0.48 +/- 0.04 vs. 0.24 +/- 0.02 ml/n, p less than 0.001). Since tissue disposition of intravenous 45Ca was not different between WKY and SHR, the increased renal excretion of calcium after oral administration in SHR, therefore, reflects increased intestinal absorption of calcium. Correction of established hypertension did not abolish the hypercalciuria. We believe that increased

  14. Clinically significant change in stroke volume in pulmonary hypertension

    NARCIS (Netherlands)

    van Wolferen, S.A.; van de Veerdonk, M.C.; Mauritz, G.J.; Jacobs, W.; Marcus, J.T.; Marques, K.M.J.; Bronzwaer, J.G.F.; Heijmans, M.W.; Boonstra, A.; Postmus, P.E.; Westerhof, N.; Noordegraaf, A.V.

    2011-01-01

    Background: Stroke volume is probably the best hemodynamic parameter because it reflects therapeutic changes and contains prognostic information in pulmonary hypertension (PH). Stroke volume directly reflects right ventricular function in response to its load, without the correction of compensatory

  15. Heterogeneity in arterial remodeling among sublines of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Bakker, Erik N. T. P.; Groma, Gergely; Spijkers, Léon J. A.; de Vos, Judith; van Weert, Angela; van Veen, Henk; Everts, Vincent; Arribas, Silvia M.; VanBavel, Ed

    2014-01-01

    Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that the pathophysiology of vascular

  16. Hypertension unawareness among Chinese patients with first-ever stroke

    Directory of Open Access Journals (Sweden)

    Qinqin Cao

    2016-02-01

    Full Text Available Abstract Background The low rates of hypertension treatment and control, partly due to its unawareness, are the main causes of the high stroke incidence in China. The purpose of this study was to evaluate hypertension unawareness amongst patients with first-ever stroke and to detect factors associated with its unawareness. Methods We selected those diagnosed with hypertension from patients with first-ever stroke registered in the Nanjing Stroke Registry Program between 2004 and 2014. These hypertensives were divided as being aware or unaware of their hypertension by using a brief questionnaire conducted shortly after the stroke. Multivariate logistic regression analysis was performed to identify potential factors associated with hypertension unawareness. Results Of the 5309 patients with first-ever stroke, 3732 (70.3 % were diagnosed with hypertension. Among which, 593 (15.9 % were unaware of their hypertension at the time of stroke onset. Lower-level of education (primary school or illiteracy and smoking were associated positively with hypertension unawareness; while advanced age, overweight, diabetes mellitus, heart diseases and family history of stroke were associated negatively with hypertension unawareness. Annual data analyzed indicated that the rate of hypertension awareness increased during the past 11 years (r = 0.613, P = 0.045 for trends. Conclusions A substantial proportion (15.9 % of Chinese patients with hypertension had not been aware of this covert risk until an overt stroke occurred. Hypertension unawareness was associated with lower educational levels and smoking, which address the importance of health education especially in these individuals.

  17. Nitric oxide synthase isoforms in spontaneous and salt hypertension

    Czech Academy of Sciences Publication Activity Database

    Hojná, Silvie; Kuneš, Jaroslav; Zicha, Josef

    2007-01-01

    Roč. 25, Suppl. 2 (2007), S 338-S 338 ISSN 0263-6352. [European Meeting on Hypertension /17./. 15.06.2007-19.06.2007, Milan] R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : nitric oxide synthase isoforms * spontaneous and salt hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  18. Spontaneous Tricuspid Valve Chordal Rupture in Idiopathic Pulmonary Hypertension.

    Science.gov (United States)

    Rodrigues, Ana Clara Tude; Afonso, José E; Cordovil, Adriana; Monaco, Claudia; Piveta, Rafael; Cordovil, Rodrigo; Fischer, Claudio H; Vieira, Marcelo; Lira-Filho, Edgar; Morhy, Samira S

    2016-03-01

    Rupture of tricuspid valve is unusual, occurring mainly in the setting of blunt trauma or endomyocardial biopsy. Spontaneous tricuspid valve chordal rupture is particularly rare. We report herein a case of a patient with severe pulmonary hypertension, on the lung transplantation waiting list, who presented with spontaneous chordal rupture, exacerbation of tricuspid insufficiency and worsening of clinical status. Diagnosis and treatment, along with possible mechanisms for this complication, are discussed. © 2015, Wiley Periodicals, Inc.

  19. Cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Charvátová, Z.; Ošťádalová, Ivana; Zicha, Josef; Kuneš, Jaroslav; Maxová, H.; Ošťádal, Bohuslav

    2012-01-01

    Roč. 61, Suppl.1 (2012), S145-S153 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : neonatal spontaneously hypertensive rats * contractile function * ischemic preconditioning * chronic hypoxia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.531, year: 2012

  20. Spontaneous Spinal Epidural Hematoma as a Potentially Important Stroke Mimic

    Directory of Open Access Journals (Sweden)

    Tetsu Akimoto

    2014-01-01

    Full Text Available Hemiparesis develops in response to a wide range of neurological disorders, such as stroke, neoplasms and several inflammatory processes. Occasionally, it may also occur due to a lesion located in the high cervical spinal cord. In this concise review, we describe the features of spontaneous spinal epidural hematoma, which should be included in the large list of stroke mimics. Various concerns regarding the diagnostic and therapeutic conundrums relating to the condition are also discussed.

  1. Protective effects and potential mechanisms of Pien Tze Huang on cerebral chronic ischemia and hypertensive stroke

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    Kwong Wing

    2010-10-01

    Full Text Available Abstract Background Stroke caused by brain ischemia is the third leading cause of adult disability. Active prevention and early treatment of stroke targeting the causes and risk factors may decrease its incidence, mortality and subsequent disability. Pien Tze Huang (PZH, a Chinese medicine formula, was found to have anti-edema, anti-inflammatory and anti-thrombotic effects that can prevent brain damage. This study aims to investigate the potential mechanisms of the preventive effects of Pien Tze Huang on brain damage caused by chronic ischemia and hypertensive stroke in rats. Methods The effects of Pien Tze Huang on brain protein expression in spontaneously hypertensive rat (SHR and stroke prone SHR (SHRsp were studied with 2-D gel electrophoresis and mass spectrometric analysis with a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/TOF tandem mass spectrometer and on brain cell death with enzyme link immunosorbent assay (ELISA and immunostaining. Results Pien Tze Huang decreased cell death in hippocampus and cerebellum caused by chronic ischemia and hypertensive stroke. Immunostaining of caspase-3 results indicated that Pien Tze Huang prevents brain cells from apoptosis caused by ischemia. Brain protein expression results suggested that Pien Tze Huang downregulated QCR2 in the electron transfer chain of mitochondria preventing reactive oxygen species (ROS damage and possibly subsequent cell death (caspase 3 assay as caused by chronic ischemia or hypertensive stroke to hippocampus and cerebellum. Conclusion Pien Tze Huang showed preventive effects on limiting the damage or injury caused by chronic ischemia and hypertensive stroke in rats. The effect of Pien Tze Huang was possibly related to prevention of cell death from apoptosis or ROS/oxidative damage in mitochondria.

  2. Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Linz Dominik

    2012-09-01

    Full Text Available Abstract Background The additive effects of obesity and metabolic syndrome on left ventricular (LV maladaptive remodeling and function in hypertension are not characterized. Methods We compared an obese spontaneously hypertensive rat model (SHR-ob with lean spontaneously hypertensive rats (SHR-lean and normotensive controls (Ctr. LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB, Serca2a and glucose transporters (GLUT1 and GLUT4 were determined by immunohistochemistry. Results Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398 but was higher when compared to Ctr (155 ± 2 mmHg, p  Conclusion In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.

  3. Management of arterial hypertension in patients with acute stroke.

    Science.gov (United States)

    Adeoye, Opeolu; Jauch, Edward C

    2006-11-01

    Management of arterial hypertension in the hyperacute period immediately after stroke ictus remains controversial. Extremes of blood pressure (BP) are associated with poor outcomes in all stroke subtypes. Severely hypertensive patients likely benefit from modest BP reductions, but aggressive BP reduction may worsen outcome. Although little evidence is currently available to definitively establish guideline recommendations for optimal BP goals at stroke presentation, recently published research is shedding some light on how to approach management of BP after stroke. Antihypertensive treatment should probably be deferred in ischemic stroke patients except in cases of severe hypertension or when thrombolytic therapy is warranted and the patient's BP is above acceptable levels. Hypertensive hemorrhagic stroke patients may benefit from modest BP reductions. Relative hypotension causing regional hypoperfusion is an increasingly understood concept immediately following ischemic or hemorrhagic stroke, emphasizing the need for careful titration of appropriate medications to minimize fluctuations in BP for treated patients. Ongoing trials will improve our current knowledge regarding BP management after ischemic and hemorrhagic stroke.

  4. Norepinephrine release in arteries of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Zsoter, T.T.; Wolchinsky, C.; Lawrin, M.; Sirko, S.

    1982-01-01

    The role of the sympathetic nervous system in arterial hypertension cannot be properly evaluated until it is known about the activity in the vessels themselves. In this study researchers investigated the effect of transmural stimulation on the tail artery - labelled in vitro with 3 H-norepinephrine - of 7-9 week old spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKR). Electrical stimulation using two frequencies (2 and 10 Hz) resulted in significantly more 3 H overflow in vessels from SHR than from WKR. With 10 Hz stimulation the fractional release was also greater. Column chromatographic analysis of 3 H overflow revealed that transmural stimulation in arteries of SHR enhanced mainly the release of norepinephrine and not of its metabolites. Significantly, an increased release of 3 H-norepinephrine on stimulation was observed in SHR before the full development of hypertension suggesting that it might be a cause rather than a consequence of high blood pressure

  5. [Risk factors of stroke among Congolese black hypertensive diabetics].

    Science.gov (United States)

    Longo-Mbenza, B; Ngimbi, R Mombo; Ngoma, D Vangu; Fuele, S Mbungu; Buassa-bu-Tsumbu, B

    2008-02-01

    The relationship between diabetes mellitus and risk of stroke is well established. This risk is more elevated for hypertensive diabetics men. To determine the incidence and the risk factors of stroke among hypertensive diabetics. This prospective study has considered baseline demographic, behavioural and biological parameters collected in 2002 among black Congolese hypertensive diabetics from Kinshasa till the onset of stroke or not in 2006. Out of 492 followed-up patients (279 women, 213 men, 57+/-10 years), 41.9% were old of age > or = 60 years, and 16.5% experienced acute stroke. In univariate analysis, a significant association between age > or = 60 years, cigarette smoking, excessive alcohol intake, diabetes duration > or = 2 years, pulse pressure > or = 60 mmHg, acute bacterian pneumonia, left ventricule hypertrophy, hypertensive retinopathy, diabetic retinopathy, diabetic foot, diabetic neuropathy, congestive heart failure, chronic renal failure, lack of diabetic treatment compliance and the occurrence of acute stroke. However, multivariate analysis identified only acute bacterian pneumonia, diabetic retinopathy, diabetic neuropathy, chronic renal failure and pulse pressure > or = 60 mmHg as the independent risk factors of stroke onset among these black congolese hypertensive diabetics with the following and respective values of relative risk (hazard ratio): 6,2 (IC 95%: 3.2 to 11.9; P<0.0001), 2,2 (IC 95%: 1.2 to 4.1; P<0.01), 3.6 (IC 95%: 1.9 to 6.8; P<0.0001), 6.4 (IC 95%: 2.9 to 14.1; P<0.01) and 4.1 (IC 95%: 1.6 to 10.3; P<0.0001). The rate of stroke onset is high among these hypertensive diabetics. This is the consequence of independent and respective action of infection, diabetic retinopathy, diabetic neuropathy, chronic renal failure and arterial stiffness.

  6. Blood pressure reduction combining baroreflex restoration for stroke prevention in hypertension in rats

    Directory of Open Access Journals (Sweden)

    Shu-Wei Song

    2010-07-01

    Full Text Available Blood pressure reduction is an important and effective strategy in stroke prevention in hypertensives. Recently, we found that baroreflex restoration was also crucial in stroke prevention. The present work was designed to test the hypothesis that a combination of blood pressure reduction and baroreflex restoration may be a new strategy for stroke prevention. In Experiment 1, the effects of ketanserin (0.3, 1, 3, 10 mg/kg, amlodipine (0.3, 1, 2, 3 mg/kg and their combination (1+0.3, 1+1, 1+2, 1+3 mg/kg on blood pressure and baroreflex sensitivity (BRS of stroke-prone spontaneously hypertensive rats (SHR-SP were determined under conscious state. It was found that both amlodipine and ketanserin decreased blood pressure dose-dependently. Ketanserin enfanced BRS from a very small dose but amlodipine enfanced BRS only at largest dose used. At the dose of 1 + 2 mg/kg (ketanserin + amlodipine, the combination possessed the largest synergism on blood pressure reduction. In Experiments 2 and 3, SHR-SP and two-kidney, two-clip (2K2C renovascular hypertensive rats received life-long treatments with ketanserin (1 mg/kg and amlodipine (2 mg/kg or their combination (0.5+1, 1+2, 2+4 mg/kg. The survival time was recorded and the brain lesion was examined. It was found that all kinds of treatments prolonged the survival time of SHR-SP and 2K2C rats. The combination possessed a significantly better effect on stroke prevention than mono-therapies. In conclusion, combination of blood pressure reduction and baroreflex restoration may be a new strategy for the prevention of stroke in hypertension.

  7. Intracerebroventricular metformin attenuates salt-induced hypertension in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Petersen, J S; Andersen, D; Muntzel, M S

    2001-01-01

    The aim of this study was to examine the effects of long-term continuous intracerebroventricular (icv) infusion of metformin on blood pressure (BP) in spontaneously hypertensive rats (SHR). To accelerate the development of hypertension, SHR were fed a 8% NaCl diet during the 3-week study period...... to hexamethonium was attenuated by all doses of metformin suggesting that chronic icv metformin decreased central sympathetic outflow. The highest doses of metformin (100 and 200 microg/day) also prevented development of hypertension, but these doses were highly neurotoxic as demonstrated by histologic evaluation...... doses of metformin attenuates hypertension and decreases the hypotensive responses to ganglionic blockade in SHR, suggesting a centrally elicited sympathoinhibitory action....

  8. Hypertensive patients using thiazide diuretics as primary stroke prevention make better functional outcome after ischemic stroke.

    Science.gov (United States)

    Shih, Hong-Mo; Lin, Wei Chun; Wang, Cheng-Hsien; Lin, Leng-Chieh

    2014-10-01

    Thiazides have been used for the control of blood pressure and primary prevention of ischemic stroke. No previous studies have assessed the influence of thiazides on functional prognosis after ischemic stroke. Demographics, prestroke conditions, poststroke National Institutes of Health Stroke Scale score, and clinical and laboratory parameters were prospectively registered in 216 Taiwanese patients. One hundred forty patients who completed follow-up 3 months after experiencing ischemic stroke were assessed with the modified Rankin scale as functional prognoses. Twenty-one patients used thiazide to control hypertension before experiencing ischemic stroke. No differences of stroke subtypes and comorbidities before stroke were observed between the 2 groups. The emergency department National Institutes of Health Stroke Scale was lesser among thiazide users (4 [2-7] versus 6 [4-16], P = .02). Among 140 patients who completed follow-up in 90 days, thiazide users had more favorable functional status (modified Rankin scale ≤2: 42.4% versus 26.9%, P = .02, odds ratio 3.34, 95%, confidence interval .130-.862). Hypertensive patients treated with thiazides long term had a lesser severity of stroke and better functional outcomes after ischemic stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Recent progress in the genetics of spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Křen, Vladimír; Landa, Vladimír; Mlejnek, Petr; Musilová, Alena; Šilhavý, Jan; Šimáková, Miroslava; Zídek, Václav

    2014-01-01

    Roč. 63, Suppl.1 (2014), S1-S8 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LL1204; GA MŠk(CZ) LH12061; GA ČR(CZ) GAP303/10/0505; GA ČR(CZ) GAP301/10/0290; GA ČR(CZ) GAP301/12/0696; GA TA ČR(CZ) TA02010013; GA MŠk(CZ) LH11049; GA ČR(CZ) GA13-04420S; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 Keywords : spontaneously hypertensive rats * genetics * hypertension * left ventricular hypertrophy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  10. Genetic analysis of metabolic defects in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Kostka, Vlastimil; Mlejnek, Petr; Křen, Vladimír; Křenová, D.; Bílá, V.; Míková, B.; Jáchymová, M.; Horký, K.; Kazdová, L.; St.Lezin, E.; Kurtz, W. T.

    2002-01-01

    Roč. 13, č. 5 (2002), s. 253-258 ISSN 0938-8990 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015; GA ČR GA305/00/1646; GA MŠk NB5299 Grant - others:NIH(US) RO1 HL56028; NIH(US) PO1 HL35018; HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : metabolic defects * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.233, year: 2002

  11. Anti-Hypertensive Effects of Acacia Polyphenol in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Nobutomo Ikarashi

    2018-03-01

    Full Text Available We have previously demonstrated that acacia polyphenol (AP exerts strong anti-obesity, anti-diabetic, and anti-atopic dermatitis effects. In the present study, we investigated the anti-hypertensive effects of AP. Spontaneously hypertensive rats (SHR with hypertension and control Wistar Kyoto rats (WKY were used. WKY and SHR were fed AP-containing food or AP-free food (control group ad libitum for 4 weeks, and their blood pressures were measured. After AP administration, both systolic and diastolic blood pressures were significantly lower in the SHR group than in the control group. There were no differences in the systolic or diastolic blood pressure of WKY between the AP group and the control group. Angiotensin-converting enzyme (ACE activity, nicotinamide adenine dinucleotide phosphate (NADPH oxidase expression, and superoxide dismutase (SOD activity in SHR kidneys were not altered by AP administration. Blood SOD activity in SHR was significantly higher in the AP group than in the control group. AP exerts anti-hypertensive effects on hypertension but has almost no effect on normal blood pressure. The anti-hypertensive effects of AP may be related to the anti-oxidative effects of increased blood SOD activity.

  12. Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Suely Tomimura

    2014-08-01

    Full Text Available Systemic arterial hypertension (SAH is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT, or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16 were randomly divided into the Laser Group (n = 8, which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8, which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group, revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group. Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

  13. Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

    Energy Technology Data Exchange (ETDEWEB)

    Tomimura, Suely, E-mail: suelytomimura@uol.com.br [Programa de Pós-Graduação em Biofotônica em Ciências da Saúde da Universidade Nove de Julho (UNINOVE) (Brazil); Silva, Bianca Passos Assumpção [Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Sanches, Iris Callado [Laboratório de Fisiologia Translacional da UNINOVE (Brazil); Canal, Marina [Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Consolim-Colombo, Fernanda [Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Unidade de Hipertensão e Central Médica de Laser do Instituto do Coração - Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HC-FMUSP), São Paulo, SP (Brazil); Conti, Felipe Fernandes; Angelis, Katia De [Laboratório de Fisiologia Translacional da UNINOVE (Brazil); Chavantes, Maria Cristina [Programa de Pós-Graduação em Biofotônica em Ciências da Saúde da Universidade Nove de Julho (UNINOVE) (Brazil); Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Unidade de Hipertensão e Central Médica de Laser do Instituto do Coração - Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HC-FMUSP), São Paulo, SP (Brazil)

    2014-08-15

    Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

  14. Intracerebroventricular metformin attenuates salt-induced hypertension in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Petersen, J S; Andersen, D; Muntzel, M S

    2001-01-01

    The aim of this study was to examine the effects of long-term continuous intracerebroventricular (icv) infusion of metformin on blood pressure (BP) in spontaneously hypertensive rats (SHR). To accelerate the development of hypertension, SHR were fed a 8% NaCl diet during the 3-week study period....... Metformin was given in the following doses: 0 (isotonic saline; n = 7), 25 (n = 8), 50 (n = 6), 100 (n = 6), and 200 microg/day icv (n = 5). Mean arterial pressure (MAP) and heart rate (HR) were measured by radiotelemetry, and as a measure of the contribution of sympathetic nerve activity to BP...... to hexamethonium was attenuated by all doses of metformin suggesting that chronic icv metformin decreased central sympathetic outflow. The highest doses of metformin (100 and 200 microg/day) also prevented development of hypertension, but these doses were highly neurotoxic as demonstrated by histologic evaluation...

  15. Activated protein C analog protects from ischemic stroke and extends the therapeutic window of tissue-type plasminogen activator in aged female mice and hypertensive rats.

    Science.gov (United States)

    Wang, Yaoming; Zhao, Zhen; Chow, Nienwen; Rajput, Padmesh S; Griffin, John H; Lyden, Patrick D; Zlokovic, Berislav V

    2013-12-01

    3K3A-activated protein C (APC) protects young, healthy male rodents after ischemic stroke. 3K3A-APC is currently under development as a neuroprotectant for acute ischemic stroke in humans. Stroke Therapy Academic Industry Roundtable recommends that after initial studies in young, healthy male animals, further studies should be performed in females, aged animals, and animals with comorbid conditions. Here, we studied the effects of delayed 3KA-APC therapy alone and with tissue-type plasminogen activator (tPA) in aged female mice and spontaneously hypertensive rats. We used Stroke Therapy Academic Industry Roundtable recommendations for ensuring good scientific inquiry. Murine recombinant 3K3A-APC (0.2 mg/kg) alone or with recombinant tPA (10 mg/kg) was given intravenously 4 hours after transient middle cerebral artery occlusion in aged female mice and rats and after embolic stroke in spontaneously hypertensive rat. 3K3A-APC was additionally administered within 3 to 7 days after stroke. The neuropathological analysis and neurological scores, foot-fault, forelimb asymmetry, and adhesive removal tests were performed within 7 and 28 days of stroke. In all models, tPA alone had no effects on the infarct volume or behavior. 3K3A-APC alone or with tPA reduced the infarct volume 7 days after the middle cerebral artery occlusion in aged female mice and embolic stroke in spontaneously hypertensive rat by 62% to 66% and 50% to 53%, respectively, significantly improved (Pmice, 3K3A-APC was protective within 4 weeks of stroke. 3K3A-APC protects from ischemic stroke and extends the therapeutic window of tPA in aged female mice and in spontaneously hypertensive rat with a comorbid condition.

  16. Clinically significant change in stroke volume in pulmonary hypertension.

    Science.gov (United States)

    van Wolferen, Serge A; van de Veerdonk, Marielle C; Mauritz, Gert-Jan; Jacobs, Wouter; Marcus, J Tim; Marques, Koen M J; Bronzwaer, Jean G F; Heymans, Martijn W; Boonstra, Anco; Postmus, Pieter E; Westerhof, Nico; Vonk Noordegraaf, Anton

    2011-05-01

    Stroke volume is probably the best hemodynamic parameter because it reflects therapeutic changes and contains prognostic information in pulmonary hypertension (PH). Stroke volume directly reflects right ventricular function in response to its load, without the correction of compensatory increased heart rate as is the case for cardiac output. For this reason, stroke volume, which can be measured noninvasively, is an important hemodynamic parameter to monitor during treatment. However, the extent of change in stroke volume that constitutes a clinically significant change is unknown. The aim of this study was to determine the minimal important difference (MID) in stroke volume in PH. One hundred eleven patients were evaluated at baseline and after 1 year of follow-up with a 6-min walk test (6MWT) and cardiac MRI. Using the anchor-based method with 6MWT as the anchor, and the distribution-based method, the MID of stroke volume change could be determined. After 1 year of treatment, there was, on average, a significant increase in stroke volume and 6MWT. The change in stroke volume was related to the change in 6MWT. Using the anchor-based method, an MID of 10 mL in stroke volume was calculated. The distribution-based method resulted in an MID of 8 to 12 mL. Both methods showed that a 10-mL change in stroke volume during follow-up should be considered as clinically relevant. This value can be used to interpret changes in stroke volume during clinical follow-up in PH.

  17. Spontaneous cerebral microbleeds on gradient echo MR imaging in the stroke patients

    International Nuclear Information System (INIS)

    Kwak, Seong Ho; Song, Chang June; Kim, Dae Bong; Jeong, Geum Chae

    2003-01-01

    To investigate the spontaneous cerebral microbleeding occurring at gradient-echo MRI, and its relationship with associated stroke lesions and risk factors. Between September 2001 and December, 2002, 32 patients (21 men and 11 women; mean age 63 years) in whom cerebral microbleeding occurred at gradient-echo MRI were retrospectively investigated. Using a 1.5T MR imager, spin-echo T1-weighted, fast spin-echo T2-weighted, diffusion-weighted, and gradient-echo images were obtained. The number and location of microbleeds seen on gradient echo images, patients data, and associated stroke lesions such as intracerebral hemorrhage and lacunar and territorial infarction were assessed. Among the 32 patients, 563 microbleeds and between 1 and 66 (mean, 17.6) were noted at gradient-echo imaging. Microbleeding occurred in the cortical/subcortical area (n=216), the basal ganglia (n=173), thalamus (n=92), cerebellum (n=41), brainstem (n=36) and corpus callosum (n=1), and in 20 patients was bilateral. Patients had a history of hypertension (n=26), hypertriglycemia (n=12), heart disease (n=4), and diabetes mellitus (n=3). Stroke lesions were seen in 27 patients, intracerebral hemorrhage in ten, lacunar infarction in 24, and territorial infarction in four. The incidence and number of microbleeds was greater in older patients and in those with hypertension, hypertriglycemia, and stroke lesions such as intracerebral hemorrhage or lacunar infarction. The detection of microbleeding at gradient-echo imaging is helpful, since it predicts the possibility of cerebral hemorrhage in these patients

  18. Spontaneous cerebral microbleeds on gradient echo MR imaging in the stroke patients

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Seong Ho; Song, Chang June; Kim, Dae Bong; Jeong, Geum Chae [Chungnam National University College of Medicine, Taejon (Korea, Republic of)

    2003-08-01

    To investigate the spontaneous cerebral microbleeding occurring at gradient-echo MRI, and its relationship with associated stroke lesions and risk factors. Between September 2001 and December, 2002, 32 patients (21 men and 11 women; mean age 63 years) in whom cerebral microbleeding occurred at gradient-echo MRI were retrospectively investigated. Using a 1.5T MR imager, spin-echo T1-weighted, fast spin-echo T2-weighted, diffusion-weighted, and gradient-echo images were obtained. The number and location of microbleeds seen on gradient echo images, patients data, and associated stroke lesions such as intracerebral hemorrhage and lacunar and territorial infarction were assessed. Among the 32 patients, 563 microbleeds and between 1 and 66 (mean, 17.6) were noted at gradient-echo imaging. Microbleeding occurred in the cortical/subcortical area (n=216), the basal ganglia (n=173), thalamus (n=92), cerebellum (n=41), brainstem (n=36) and corpus callosum (n=1), and in 20 patients was bilateral. Patients had a history of hypertension (n=26), hypertriglycemia (n=12), heart disease (n=4), and diabetes mellitus (n=3). Stroke lesions were seen in 27 patients, intracerebral hemorrhage in ten, lacunar infarction in 24, and territorial infarction in four. The incidence and number of microbleeds was greater in older patients and in those with hypertension, hypertriglycemia, and stroke lesions such as intracerebral hemorrhage or lacunar infarction. The detection of microbleeding at gradient-echo imaging is helpful, since it predicts the possibility of cerebral hemorrhage in these patients.

  19. Spontaneous Cervical Epidural Hematoma with Hemiparesis Mimicking Cerebral Stroke

    Directory of Open Access Journals (Sweden)

    Mehmet Tiryaki

    2014-01-01

    Full Text Available Aim. Spontaneous cervical epidural hematoma (SCEH is defined as an epidural hematoma that does not have an etiological explanation. The most common site for SCEH is cervicothoracic area. Early diagnosis and treatment are important for prognosis and good results. In this paper, we aimed to present a case who complains of sudden weakness on right extremities imitating cerebral stroke and that neuroimaging reveals spontaneous cervical epidural hematoma. Case. A 72-year-old woman was admitted to our hospital with acute neck pain and loss of strength on right extremities. On neurological examination, the patient had right hemiparesis. PT, aPTT, and INR results were 50.5, 42.8, and 4.8, respectively. Cranial MRI was in normal limits. Spinal MRI revealed a lesion that extends from C4 to C7 located on the right side and compatible with epidural hematoma. The patient was operated after normalization of INR values. Conclusion. Even though SCEH is a rare condition, it can cause severe morbidity and mortality. Early diagnosis and treatment are quiet important for prognosis. SCEH can easily be mistaken for stroke as with other pathologies and this diagnosis should come to mind especially in patients who have diathesis of bleeding.

  20. A Case of Spontaneous Spinal Epidural Hematoma Mimicking Stroke

    Directory of Open Access Journals (Sweden)

    Emine Rabia Koç

    2014-09-01

    Full Text Available Spontaneous spinal epidural hematoma is an uncommon cause of acute non-traumatic myelopathy and may present with various clinical phenotypes. Focal neurological symptoms can result in overlooking this differential diagnosis in patients presenting with neurological deficits and assuming the diagnosis of a stroke. Therefore, a thorough documentation of patient history is of great importance, since this can reveal symptoms suggestive of a different etiology. Here, we present a case of an 80-year-old female who was admitted with a hemiparesis without cortical or cranial neurological abnormalities. She mentioned of preceding shoulder and neck pain. Diagnosis of epidural hematoma was made by cervical magnetic resonance imaging. Symptoms resolved partially after surgical intervention. Our case illustrates the variation in the clinical presentation of spontaneous spinal epidural hematoma which can be misdiagnosed as stroke. Therefore, in patients with preceding neck, shoulder or interscapular pain and focal neurological deficits, this diagnosis should be included in the differential, particularly when cortical and cranial signs are lacking

  1. Hypertension, hemorrhagic stroke and smoking cessation

    OpenAIRE

    Reverte Bernal, María Perpetuo Socorro; Aparicio-Erroz, Sergio; López de la Fuente, Raquel

    2003-01-01

    Smoking cessation is considered as a good solution for stroke prevention. Unfortunately, first-line therapies to reduce cigarette smoking are not always useful. Some clinical effects of these drugs are able to produce cardiovascular adverse events. El artículo trata sobre la hipertensión arterial, las enfermedades cerebrovasculares y el hecho de dejar de fumar.

  2. Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing.

    Directory of Open Access Journals (Sweden)

    Dennis H Lau

    Full Text Available BACKGROUND: Both ageing and hypertension are known risk factors for atrial fibrillation (AF although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR. METHODS: SHR were studied at 12 and 15 months of age (n = 8 per group together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY. Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP, atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. RESULTS: COMPARED TO WKY CONTROLS, THE SHR DEMONSTRATED: Higher systolic blood pressure (p<0.0001, bi-atrial enlargement (p<0.05, bi-ventricular hypertrophy (p<0.05, lower atrial ERP (p = 0.008, increased atrial conduction heterogeneity (p = 0.001 and increased atrial interstitial fibrosis (p = 0.006 & CD68-positive macrophages infiltration (p<0.0001. These changes resulted in higher atrial arrhythmia inducibility (p = 0.01 and longer induced AF episodes (p = 0.02 in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01 and atrial conduction heterogeneity (p<0.01 without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. CONCLUSIONS: Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria.

  3. Abnormalities of glucose metabolism in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Gouveia L.M.F.B.

    2000-01-01

    Full Text Available Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose metabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-³H]-glucose and gluconeogenetic activity was measured during continuous [14C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 ± 6.5 µM than in the control group (70.4 ± 3.6 µM. Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 ± 0.55 vs 9.52 ± 0.80 mg kg-1 min-1 in controls. Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals.

  4. Regional brain catecholamine levels and the development of hypertension in the spontaneously hypertensive rat: the effect of 6-hydroxydopamine

    NARCIS (Netherlands)

    Jong, Wybren de; Buuse, M. van den; Kloet, E.R. de; Versteeg, D.H.G.

    1984-01-01

    To investigate the role of central catecholaminergic pathways in the development of hypertension in the spontaneously hypertensive rat (SHR) the effects of intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) were compared with those of local injections near the main ascending

  5. Streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats: a pathophysiological model for the combined effects of hypertension and diabetes

    NARCIS (Netherlands)

    Pijl, A. J.; van der Wal, A. C.; Mathy, M. J.; Kam, K. L.; Hendriks, M. G.; Pfaffendorf, M.; van Zwieten, P. A.

    1994-01-01

    The present study was undertaken to investigate the combined effects of hypertension and streptozotocin-induced diabetes mellitus in the rat. Accordingly, four groups of rats were studied: Wistar Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR) and diabetic SHR, respectively.

  6. NEUROPROTECTIVE EFFICACY OF SUBCUTANEOUS INSULIN-LIKE GROWTH FACTOR-I ADMINISTRATION IN NORMOTENSIVE AND HYPERTENSIVE RATS WITH AN ISCHEMIC STROKE

    NARCIS (Netherlands)

    de Geyter, D.; Stoop, W.; Sarre, S.; de Keyser, J.; Kooijman, R.

    2013-01-01

    The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were

  7. Quantitative proteome of medulla oblongata in spontaneously hypertensive rats.

    Science.gov (United States)

    Sun, Dongmei; Cheng, Yu; Zhou, Danfeng; Liu, Tanshu; Chen, Shaoqin; Liang, Jing; Tang, Chunzhi; Lai, Xinsheng

    2013-01-04

    We performed an extensive quantitative proteomic analysis on the pooled medulla sample of the 11-week-old spontaneously hypertensive rats (SHR) compared to age-matched normotensive Wistar rats, using iTRAQ technology coupled with nano two-dimentional liquid chromatography followed by high resolution mass spectrometric abundance indexes techniques. Many differentially expressed proteins identified were involved in energy metabolism, such as mitochondrial part, pyruvate dehydrogenase complex, and respiratory chain. These proteins were included in citrate cycle (TCA cycle), pyruvate metabolism and oxidative phosphorylation. The proteomic analysis and subsequent Western blotting on two independent cohorts of animials indicated that the dysregulation of energy metabolism existed in the medulla of the SHR rats. The differentially expressed proteins in the dysregulation of energy metabolism in the medulla of SHR rats included down-regulated ATP6V1D, ATP6VOA1, ATP5L, DLD proteins and up-regulated AK1 protein. MAO-A protein also exhibited decreased regulation, as well as the other 3 above-mentioned energy-relative proteins (ATP6V1D, ATP5L and DLD proteins) belonging to the heterocycle metabolic process. A receiver operating characteristic curve (ROC) analysis on 4 of the differentially expressed proteins respectively resulted in an area under the receiver operating characteristic curve (AUC) of 0.95, 0.90, 0.92, and 0.81 for differentiating the SHR rats from the normotensive rats. This dysfunction in energy metabolism localizes to the medulla, the lower part of brain stem, and is, therefore, likely to contribute to the development, as well as to pathophysiological complications of hypertension.

  8. Resistant hypertension, patient characteristics, and risk of stroke.

    Directory of Open Access Journals (Sweden)

    Chen-Ying Hung

    Full Text Available Little is known about the prognosis of resistant hypertension (RH in Asian population. This study aimed to evaluate the impacts of RH in Taiwanese patients with hypertension, and to ascertain whether patient characteristics influence the association of RH with adverse outcomes.Patients aged ≥45 years with hypertension were identified from the National Health Insurance Research Database. Medical records of 111,986 patients were reviewed in this study, and 16,402 (14.6% patients were recognized as having RH (continuously concomitant use of ≥3 anti-hypertensive medications, including a diuretic, for ≥2 years. Risk of major adverse cardiovascular events (MACE, a composite of all-cause mortality, acute coronary syndrome, and stroke [included both fatal and nonfatal events] in patients with RH and non-RH was analyzed. A total of 11,856 patients experienced MACE in the follow-up period (average 7.1±3.0 years. There was a higher proportion of females in the RH group, they were older than the non-RH (63.1 vs. 60.5 years patients, and had a higher prevalence of cardiovascular co-morbidities. Overall, patients with RH had higher risks of MACE (adjusted HR 1.17; 95%CI 1.09-1.26; p<0.001. Significantly elevated risks of stroke (10,211 events; adjusted HR 1.17; 95%CI 1.08-1.27; p<0.001, especially ischemic stroke (6,235 events; adjusted HR 1.34; 95%CI 1.20-1.48; p<0.001, but not all-cause mortality (4,594 events; adjusted HR 1.06; 95%CI 0.95-1.19; p = 0.312 or acute coronary syndrome (2,145 events; adjusted HR 1.17; 95%CI 0.99-1.39; p = 0.070 were noted in patients with RH compared to those with non-RH. Subgroup analysis showed that RH increased the risks of stroke in female and elderly patients. However, no significant influence was noted in young or male patients.Patients with RH were associated with higher risks of MACE and stroke, especially ischemic stroke. The risks were greater in female and elderly patients than in male or young

  9. Proteomic response to acupuncture treatment in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Xinsheng Lai

    Full Text Available Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3 acupoint in spontaneously hypertensive rats (SHRs. Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7(th day, rat medullas were dissected, homogenized, and subject to 2D gel electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure stabilized after the 5th day of acupuncture, and compared with non-acupoint treatment, Taichong-acupunctured rat's systolic pressure was reduced significantly (P<0.01, though not enough to bring blood pressure down to normal levels. The different treatment groups also showed differential protein expression: the 2D images revealed 571 ± 15 proteins in normal SD rats' medulla, 576 ± 31 proteins in SHR's medulla, 597 ± 44 proteins in medulla of SHR after acupuncturing Taichong, and 616 ± 18 proteins in medulla of SHR after acupuncturing non-acupoint. In the medulla of Taichong group, compared with non-acupoint group, seven proteins were down-regulated: heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1, DJ-1 protein and superoxide dismutase. The altered expression of several proteins by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The results indicate an increase in antioxidant enzymes in the medulla of the SHRs subject to acupuncture, which may provide partial explanation for the antihypertensive effect of acupuncture

  10. The effect of recombinant aminopeptidase A (APA) on hypertension in pregnant spontaneously hypertensive rats (SHRs).

    Science.gov (United States)

    Ishii, Masakazu; Hattori, Akira; Numaguchi, Yasushi; Ma, Xiuyang; Nagasaka, Tetsuro; Tsujimoto, Masafumi; Murohara, Toyoaki; Kobayashi, Hiroshi; Mizutani, Sigehiko

    2009-09-01

    We have tested the effects of aminopeptidase A (APA), MgSO(4) and various conventional antihypertensive drugs on hypertension in pregnant spontaneously hypertensive rats (SHRs) and examined the effects on both fetal heart and kidney. We used recombinant human APA, which has been recently shown to work as an antihypertensive agent in SHRs (n=5). Each drug was administered from gestational day 10 to day 20 and each dose was increased daily up to 10 fold until the end of treatment except for MgSO(4) (n=5 per each group). Blood pressure (BP) was monitored and fetal kidneys and heart were histologically examined. The antihypertensive effects of the drugs were in the following order: hydralazine>aminopeptidase A and angiotensin receptor blockers (ARBs), candesartan>MgSO(4) and methyldopa. Microscopic examination showed that fetal exposure to candesartan is associated with poor proximal tubular differentiation in the kidney and that to MgSO(4) is associated with poor blood vessel formation in the heart, respectively. Our present study showed that APA is one of the candidates for antihypertensive agents in hypertension during pregnancy.

  11. Calcium and vitamin D metabolism in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Hsu, Chen Hsing; Yang, Chweishiun; Patel, S.R.; Stevens, M.G.

    1987-01-01

    The authors have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites, measured by radioreceptor assay and radioimmunoassay in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol [1,25(OH) 2 D 3 ] concentration of WKY was similar to the level of SHR. Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH) 2 D 3 of SHR was significantly lower than that of WKY. Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY and SHR. The SHR, but not the WKY, developed hypocalcemia. Despite hypocalcemia, fasting urinary Ca 2+ excretion of SHR exceeded that of WKY. They conclude that the lower 1,25(OH) 2 D 3 level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH) 2 D 3 . The low level of 1,25(OH) 2 D 3 is associated with renal wasting of calcium and hypocalcemia in SHR

  12. Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Ribeiro, Rachel Melo; Pinheiro Neto, Vicente Férrer; Ribeiro, Kllysmann Santos; Vieira, Denilson Amorim; Abreu, Iracelle Carvalho; Silva, Selma do Nascimento; Cartágenes, Maria do Socorro de Sousa; Freire, Sônia Maria de Farias; Borges, Antonio Carlos Romão; Borges, Marilene Oliveira da Rocha

    2014-01-01

    This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

  13. Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rachel Melo Ribeiro

    2014-01-01

    Full Text Available This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC in normotensive Wistar rats and in spontaneously hypertensive rats (SHR, as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01–4.0 mg/kg in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day, orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (Emax⁡ of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL. This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

  14. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE

    Science.gov (United States)

    SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE.PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti. US EPA, ORD, NHEERL, ETD, PTB, Research Triangle Park, NC USA. Environmental particles (PM...

  15. Spontaneous swallow frequency compared with clinical screening in the identification of dysphagia in acute stroke.

    Science.gov (United States)

    Crary, Michael A; Carnaby, Giselle D; Sia, Isaac

    2014-09-01

    The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Biological response of spontaneously hypertensive rats to the streptozotocin administration

    Directory of Open Access Journals (Sweden)

    Virginia Alice Vieira da Costa

    2008-02-01

    Full Text Available The sensitivity of adult spontaneously hypertensive rats (SHR to the diabetogenic effect of streptozotocin (STZ was studied. The animals were subdivided into three groups: control (citrate buffer, streptozotocin 40 mg/kg or 50 mg/kg, and general biologic parameters were analyzed, in addition to systolic blood pressure, blood glucose and insulin levels determinations. Both doses were able to induce hyperglycemia above 300 mg/dl; however, 50 mg/kg provoked a more pronounced physiological alterations in body weight, diuresis, water and food intake. There was no change on systolic blood pressure with either dose. Results suggested that SHRs did not need doses of streptozotocin above 40mg/kg in order to produce diabetes probably because this strain was much more sensible than normotensive rats. In addition, streptozotocin might be a drug choice to induce diabetes without provoking alterations in the blood pressure which allowed the use of this experimental model in the studies of induced hypertension-diabetes.Foi estudada a sensibilidade de ratos espontaneamente hipertensos (SHR adultos ao efeito diabetogênico da estreptozotocina (STZ. Os animais foram subdivididos em grupos: controle (tampão citrato, 40 mg/kg ou 50 mg/kg de estreptozotocina, sendo analisados parâmetros biológicos gerais, pressão arterial sistólica, níveis sanguíneos de glicose e insulina. Ambas doses foram capazes de induzir hiperglicemia acima de 300 mg/dl, entretanto a dose de 50 mg/kg provocou efeitos fisiológicos mais pronunciados no peso corpóreo, diurese, ingestão hídrica e de ração. Não houve alteração da pressão arterial sistólica em qualquer dose. Nossos achados sugerem que SHRs não necessitam de doses de estreptozotocina acima de 40 mg/kg com para produzir diabetes, provavelmente porque essa cepa é muito mais sensível do que ratos normotensos. A estreptozotocina pode ser a droga de escolha para induzir diabetes sem provocar alterações na press

  17. Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

    Science.gov (United States)

    Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

    2013-12-01

    Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

  18. Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

    Science.gov (United States)

    Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

    2014-01-01

    Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

  19. Impact of Achieved Blood Pressure on First Stroke in Uncomplicated Grade 1 Hypertension.

    Science.gov (United States)

    Qin, Xianhui; Li, Youbao; Sun, Ningling; He, Mingli; Tang, Genfu; Yin, Delu; Wang, JiGuang; Liang, Min; Wang, Binyan; Huo, Yong; Xu, Xin; Xu, Xiping; Hou, Fan Fan

    2017-03-08

    We aimed to test the impact of achieved blood pressure (BP) on first stroke among patients with grade 1 hypertension and without cardiovascular diseases in the China Stroke Primary Prevention Trial. A total of 3187 patients with uncomplicated grade 1 hypertension were included. The risk of outcomes was assessed according to: (1) the proportion of visits in which BP was reduced to hypertension subtypes (isolated systolic hypertension or systolic-diastolic hypertension). However, a time-averaged SBP hypertension. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  20. On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats

    NARCIS (Netherlands)

    Michel, M. C.; Jäger, S.; Casto, R.; Rettig, R.; Graf, C.; Printz, M.; Insel, P. A.; Philipp, T.; Brodde, O. E.

    1992-01-01

    We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor

  1. Chronic effects of arotinolol (S-596) in spontaneously hypertensive rats.

    Science.gov (United States)

    Kishi, K; Kawashima, K; Sokabe, H; Saito, K

    1985-01-01

    Arotinolol (S-596, ARL) is a beta-adrenoceptor blocking drug with weak alpha-adrenoceptor blocking activity, and may be classified into the fourth generation. Antihypertensive effects of ARL were studied for 12 weeks in spontaneously hypertensive (SHR) rats. Propranolol (PPL) was used as the reference drug. ARL (20 and 100 mg/kg per day, p.o.) and PPL (100 mg/kg per day, p.o.) treatments significantly decreased heart rate, within a week after the drug treatments had started and thereafter. Tail blood pressure (BP), determined by prewarming the rat at 50 degrees C for 3 min, was slightly higher in the two ARL treated groups than in the control. Tail BP was slightly lower in the PPL treated group than in the control. Mean BP determined directly at the 12th week was lower in the two ARL and PPL groups than in the control by more than 20 mmHg. Both ARL (100 mg/kg per day) and PPL (100 mg/kg per day) treatments significantly reduced incidences of the vascular lesions, and also prevented the decrease of kidney weights usually associated with mild vascular lesions. Furthermore, these treatments showed a tendency to decrease plasma renin (PRC) and aldosterone (PAC) concentrations determined 20 h after the last administration. As mean BP must be more reliable than tail BP, it was concluded that ARL (20 and 100 mg/kg per day) showed almost the same chronic antihypertensive activity in SHR rats as PPL (100 mg/kg per day). Preventive effects of ARL on development of vascular lesions also supported the above view.

  2. Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Hye Suk Hwang

    2011-01-01

    Full Text Available Using spontaneously hypertensive rats (SHR, this study investigated whether electroacupuncture (EA could reduce early stage hypertension by examining nitric oxide (NO levels in plasma and nitric oxide synthase (NOS levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20 or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS and neuronal NOS (nNOS protein expression in the mesenteric artery. Systolic blood pressure (SBP and diastolic blood pressure (DBP were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.

  3. Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

    Directory of Open Access Journals (Sweden)

    Philip M. Coan

    2017-03-01

    Full Text Available We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR and Wistar Kyoto (WKY rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the

  4. Cerebrovascular Gene Expression in Spontaneously Hypertensive Rats After Transient Middle Cerebral Artery Occlusion

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Mostajeran, Maryam; Frederiksen, Simona Denise

    2017-01-01

    the pathological mechanisms set in play after stroke. Verified by quantitative PCR, expression of Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 was significantly increased in the occluded compared to non-occluded MCAs from both SHRs and WKY rats. Additionally, expression of Mmp9, Icam1, Hif1α and Timp1 was increased......Hypertension is a major risk factor for stroke, which is one of the leading global causes of death. In the search for new and effective therapeutic targets in stroke research, we need to understand the influence of hypertension in the vasculature following stroke. We used Affymetrix whole...... suggest that Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 may be possible mediators of the vascular changes in the occluded MCAs from both SHRs and WKY rats after tMCAO. The aforementioned genes possess biological functions that are consistent with early stroke injuries. In conclusion, these genes may...

  5. Characterizing operant hyperactivity in the Spontaneously Hypertensive Rat

    Directory of Open Access Journals (Sweden)

    Hill Jade C

    2012-01-01

    Full Text Available Abstract Background Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR, the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses. Method Male SHR, Wistar-Kyoto (WKY and Wistar rats (WIS were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s between post-natal days (PND 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of response-reinforcement functions (Herrnstein's hyperbola and bout-organized behavior were estimated in each epoch. Results SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute, and particularly in the second epoch. Estimates of Herrnstein's hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential. Across epochs and schedules, a more detailed analysis of response bouts by SHR revealed that these were shorter than those by WKY, but more frequent than those by WKY and WIS. Differences in bout length subsided between epochs, but differences in bout-initiation rate were exacerbated. These results were interpreted in light of robust evidence linking changes in bout-organization parameters and experimental manipulations of motivation and response-reinforcement contingency. Conclusions Operant hyperactivity in SHR was confirmed. Although incentive

  6. Spontaneous Low Frequency Oscillations in Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Phillip, Dorte; Schytz, Henrik Winther; Iversen, Helle Klingenberg

    2014-01-01

    patients admitted to the stroke unit with symptoms of ischemic stroke. 11/29 patients received thrombolytic therapy. NIRS examination was conducted 2 days (median time) from stroke onset. NIRS optodes were placed on each side of the head with a 3 cm source-detector distance. Using transfer function...

  7. Chronic Management of Hypertension after Stroke: The Role of Ambulatory Blood Pressure Monitoring

    Science.gov (United States)

    Castilla-Guerra, Luis; Fernandez-Moreno, Maria del Carmen

    2016-01-01

    Hypertension is the most important potentially reversible risk factor for stroke in all age groups; high blood pressure (BP) is also associated with increased risk of recurrent stroke in patients who have already had an ischemic or hemorrhagic event. Twenty-four hour ambulatory BP monitoring (ABPM) has become an important tool for improving the diagnosis and management of hypertension, and is increasingly used to assess patients with hypertension. Nevertheless, although ABPM devices are increasingly used for assessment of hypertension, their value in the chronic management of hypertension in patients with stroke has not been systematically studied. In fact, among large-scale randomized trials for secondary stroke prevention, only the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention trial included 24-hour ABPM. ABPM has demonstrated chronic disruption of the circadian rhythm of BP after acute phase of stroke and has shown higher sensitivity compared to office BP in evaluating the effectiveness of antihypertensive treatment among stroke survivors. High 24-hour BP is an independent predictor for cerebrovascular events, brain microbleeds, and subsequent development of dementia. Nevertheless, although stroke care guidelines endorse the importance of hypertension management, the specific role of ABPM among stroke survivors after the acute phase of disease has not been established. Further studies are needed to clarify whether routine application of ABPM among these patients should be recommended. PMID:26687120

  8. Post-stroke treatment with 17β-estradiol exerts neuroprotective effects in both normotensive and hypertensive rats.

    Science.gov (United States)

    Stoop, Wendy; De Geyter, Deborah; Verachtert, Sofie; Brouwers, Sofie; Verdood, Peggy; De Keyser, Jacques; Kooijman, Ron

    2017-04-21

    Although ischemic stroke is a major cause of death worldwide and the predominant cause of acquired disability, the only effective drug therapy that has been developed thus far is reperfusion by tissue plasminogen activator. Since most patients do not qualify for this treatment, new methods have to be developed. It is well known that estradiol (E 2 ) exerts neuroprotective effects in different models of cerebral ischemia, but post-stroke treatment after an acute stroke has hardly been investigated. As many patients with an acute ischemic stroke have arterial hypertension, it is also of interest to evaluate the influence of this co-morbidity on the treatment efficacy of E 2 . The effects of E 2 administered 30min after a transient middle cerebral artery occlusion (tMCAO) induced by an intracerebral injection of endothelin-1 were assessed in male normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Treatment with E 2 reduced infarct size in both WKY and SHRs and decreased the number of degenerating neurons, indicating that acute treatment with E 2 is indeed neuroprotective. To address the role of glia in neuroprotection, the effects of E 2 on the activation of microglia and astrocytes was determined. It appeared that E 2 had no effect on microglial activation, but reduced the activation of astrocytes in SHRs but not in the normotensive controls. We conclude that post-stroke E 2 treatment in both normotensive and hypertensive rats is neuroprotective. Although the presence of hypertension changed the astrocytic response to E 2 , it did not affect treatment efficacy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Hospital treatment costs and length of stay associated with hypertension and multimorbidity after hemorrhagic stroke.

    Science.gov (United States)

    Specogna, Adrian V; Turin, Tanvir C; Patten, Scott B; Hill, Michael D

    2017-08-10

    Previous studies have identified various treatment and patient characteristics that may be associated with higher hospital cost after spontaneous intracerebral hemorrhage (ICH); a devastating type of stroke. Patient morbidity is perhaps the least understood of these cost-driving factors. We describe how hypertension and other patient morbidities affect length of stay, and hospital treatment costs after ICH using primary and simulated data. We also describe the relationship between cost and length of stay within these patients. We used a cohort design; evaluating 987 consecutive ICH patients across one decade in a Canadian center. Economic, treatment, and patient data were obtained from clinical and administrative sources. Multimorbidity was defined as the presence of one or more diagnoses at hospital admission in addition to a primary diagnosis of ICH. Hypertension was the most frequent (67%) morbidity within these patients, as well as the strongest predictor of longer stay (adjusted RR for >7 days: 1.31, 95% CI: 1.07-1.60), and was significantly associated with higher cost per visit when accounting for other morbidities (adjusted cost increase for hypertension $8123.51, 95% CI: $4088.47 to $12,856.72 USD). A Monte Carlo simulation drawing one million samples of patients estimated for a generation (100 years) assuming 0.94% population growth per year, and a hospitalization rate of 12 per 100,000 inhabitants, supported these findings (p = 0.516 for the difference in unadjusted cost: simulated vs primary). Using a restricted cubic spline, we observed that the rate of change in overall cost for all patients was greatest for the first 3 weeks (p < 0.001) compared to subsequent weeks. Patient multimorbidity, specifically hypertension, is a strong predictor of longer stay and cost after ICH. The non-linear relationship between cost and time should also be considered when forecasting healthcare spending in these patients.

  10. The effect of antioxidants on the nitric oxide balance and prevention of spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, O.; Kojšová, S.; Paulis, L.; Janega, P.; Zicha, Josef; Dobešová, Zdenka; Kuneš, Jaroslav; Šimko, F.; Andriantsitohaina, R.

    2005-01-01

    Roč. 23, č. S2 (2005), S232-S232 ISSN 0263-6352. [European Meeting on Hypertension /15./. 17.06.2005-21.06.2005, Milan] Grant - others:VEGA(SK) 2/3185/24; VEGA(SK) 1/0532/03; APVT(SK) 51-017902; APVT(SK) 51-013802 Keywords : antioxidants * nitric oxide * spontaneous hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  11. Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Mancini, M.; Petretto, E.; Kleinert, C.; Scavone, A.; De, T.; Cook, S.; Šilhavý, Jan; Zídek, Václav; Pravenec, Michal; d´Amati, G.; Camici, P.G.

    2013-01-01

    Roč. 108, č. 1 (2013), s. 316 ISSN 0300-8428 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : arterial hypertension * coronary circulation * myocardial ischemia * spontaneously hypertensive rat * recombinant inbred strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.955, year: 2013

  12. Plzf as a Candidate Gene Predisposing the Spontaneously Hypertensive Rat to Hypertension, Left Ventricular Hypertrophy, and Interstitial Fibrosis

    Czech Academy of Sciences Publication Activity Database

    Liška, F.; Mancini, M.; Krupková, M.; Chylíková, B.; Křenová, D.; Šeda, O.; Šilhavý, Jan; Mlejnek, Petr; Landa, Vladimír; Zídek, Václav; d´Amati, G.; Pravenec, Michal; Křen, Vladimír

    2014-01-01

    Roč. 27, č. 1 (2014), s. 99-106 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP301/10/0756; GA ČR(CZ) GAP301/12/0696; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Grant - others:Univerzita Karlova(CZ) PRVOUK-P25/LF1/2 Institutional support: RVO:67985823 Keywords : hypertension * left ventricular hypertrophy * myocardial interstitial fibrosis * spontaneously hypertensive rat * Plzf (promyelocytic leukemia zinc finger) gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.852, year: 2014

  13. Hypertension and diabetes mellitus as a predictive risk factors for stroke.

    Science.gov (United States)

    Alloubani, Aladeen; Saleh, Abdulmoneam; Abdelhafiz, Ibrahim

    2018-03-19

    Stroke is becoming a major challenge in healthcare systems, and this has necessitated the study of the various risk factors. As the number of people with hypertension, diabetes mellitus and obesity increases, the problem is expected to worsen. This review paper evaluates what can be done to eliminate or reduce the risk of stroke. The aim of the research is to evaluate the risk factors for stroke. The paper also aims to understand how these risks can be handled to avoid incidences of stroke. Published clinical trials of stroke risk factors studies were recognised by a search of EMBASE and MEDLINE databases with keywords hypertension, blood pressure, diabetes mellitus, stroke or cardiovascular disease, or prospective study, and meta-analysis. The findings of this review are that the prevention of stroke starts with identifying risk factors for stroke, most of the patients diagnosed with stroke have various risk factors. Consequently, it is a very significant to identify all the risk factors for stroke as well as to teach the patient how to dominate them. after summarising all the studies mentioned in the paper, it can be established that hypertension and diabetes mellitus are a stroke risk factors and correlated in patients with atherosclerosis. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  14. Association Between Markers of Inflammation and Total Stroke by Hypertensive Status Among Women

    Science.gov (United States)

    Rexrode, Kathryn M.; Kotler, Gregory; Everett, Brendan M.; Glynn, Robert J.; Lee, I-Min; Buring, Julie E.; Ridker, Paul M.; Sesso, Howard D.

    2016-01-01

    BACKGROUND Markers of systemic inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule 1 [sICAM-1], and fibrinogen) have been associated with a greater risk of total and ischemic stroke, in addition to elevated blood pressure. However, the role of these inflammatory markers on stroke pathophysiology by hypertension status is uncertain. METHODS Blood samples were collected and assayed for hsCRP, sICAM-1, and fibrinogen among 27,330 initially healthy women from the Women’s Health Study, and women were followed up from 1992 to 2013. Prior to randomization, the baseline questionnaire collected self-reported hypertension status, cardiovascular risk factors, and lifestyle factors. New cases of total, ischemic, and hemorrhagic stroke were updated annually through questionnaires and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models estimated overall associations between each inflammatory marker and stroke and separately stratified by hypertension status. RESULTS We observed 629 incident total strokes over 477,278 person-years. In adjusted analyses, extreme quartiles of hsCRP and sICAM-1 were each associated with a significantly greater risk of total stroke (hsCRP: hazard ratios [HR] = 1.77, 95% confidence interval [CI]: 1.39–2.26; sICAM-1: HR = 1.28, 95% CI: 1.00–1.63). Fibrinogen was not associated with a significantly greater stroke risk. In analyses stratified by hypertension status, elevated hsCRP was associated with a nonstatistically significant greater risk of total stroke among prehypertensive and hypertensive women. CONCLUSIONS These data indicate that hsCRP and sICAM-1 are associated with hypertension status and stroke risk among women. Further work should examine the role of inflammatory markers on ischemic stroke subtypes and clarify mechanisms. PMID:27235695

  15. Heart rate as a predictor of stroke in high-risk, hypertensive patients with previous stroke or transient ischemic attack.

    Science.gov (United States)

    Sandset, Else Charlotte; Berge, Eivind; Kjeldsen, Sverre E; Julius, Stevo; Holzhauer, Björn; Krarup, Lars-Henrik; Hua, Tsushung A

    2014-01-01

    Risk factors for first stroke are well established, but less is known about risk factors for recurrent stroke. In the present analysis, we aimed to assess the effect of heart rate and other possible predictors of stroke in a hypertensive population with previous stroke or transient ischemic attack (TIA). The Valsartan Antihypertensive Long-Term Use Evaluation trial was a multicentre, double-masked, randomized controlled, parallel group trial comparing the effects of an angiotensin receptor blocker (valsartan) and a calcium channel blocker (amlodipine) in patients with hypertension and high cardiovascular risk. We used Cox proportional hazard models to investigate the effect of baseline variables on the risk of stroke. Quadratic terms of the continuous variables were entered in the models to test for linearity. Of 15,245 patients included in the trial, 3014 had a previous stroke or TIA at baseline and were included in the present analysis. Stroke recurrence occurred in 239 patients (7.9%) during a median of 4.5 years of follow-up. Resting heart rate (per 10 beats per minute; hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.18-6.58) and diabetes mellitus at baseline (HR, 1.47; 95% CI, 1.03-2.10) were significantly associated with an increased risk of stroke recurrence in the multivariable analysis. In high-risk, hypertensive patients with previous stroke or TIA, resting heart rate was the strongest predictor of recurrent stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Genetic regulation of catecholamine synthesis, storage and secretion in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Jirout, M. L.; Friese, R. S.; Mahapatra, N. R.; Mahata, M.; Taupenot, L.; Mahata, S. K.; Křen, V.; Zídek, Václav; Fischer, J.; Maatz, H.; Ziegler, M. G.; Pravenec, Michal; Hubner, N.; Aitman, T. J.; Schork, N. J.; O´Connor, D. T.

    2010-01-01

    Roč. 19, č. 13 (2010), s. 2567-2580 ISSN 0964-6906 R&D Projects: GA AV ČR(CZ) IAA500110604 Grant - others:HHMI(US) HHMI Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneously hypertensive rat * catecholamines * blood pressure Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.058, year: 2010

  17. Vascular reactivity of arteria femoralis in adult and aged spontaneously hypertensive and Wistar-Kyoto rats

    Czech Academy of Sciences Publication Activity Database

    Petrová, M.; Líšková, Silvia; Vojtko, R.; Villaris, R.; Varga, Z.; Zicha, Josef; Kristová, V.

    2013-01-01

    Roč. 114, č. 10 (2013), s. 553-555 ISSN 0006-9248 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : spontaneously hypertensive rats * Wistar-Kyoto rats * acetylcholine * norepinephrine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 0.446, year: 2013

  18. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Škop, V.; Trnovská, J.; Oliyarnyk, O.; Marková, I.; Malínská, H.; Kazdová, L.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Kůdela, M.; Pravenec, Michal; Šilhavý, Jan

    2016-01-01

    Roč. 65, č. 6 (2016), s. 891-899 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT14325 Institutional support: RVO:67985823 Keywords : fenofibrate * rosuvastatin * C-reactive protein * transgenic * spontaneously hypertensive rat * inflammation * hepatotoxic Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.461, year: 2016

  19. One-Week Antihypertensive Effect of Ile-Gln-Pro in Spontaneously Hypertensive Rats

    NARCIS (Netherlands)

    Lu, Jun; Sawano, Yoriko; Miyakawa, Takuya; Xue, You-Lin; Cai, Mu-Yi; Egashira, Yukari; Ren, Di-Feng; Tanokura, Masaru

    2011-01-01

    The antihypertensive effect of an angiotensin I-converting enzyme (ACE) inhibitory peptide lie-Gin-Pro (IQP), whose sequence was derived from Spirulina platensis, was investigated in spontaneously hypertensive rats (SHRs) for 1 week. The weighted systolic blood pressure (SBP) and diastolic blood

  20. Comparison of vascular function and structure of iliac artery in spontaneously hypertensive and hereditary hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Čačányiová, S.; Cebová, M.; Kuneš, Jaroslav; Kristek, F.

    2006-01-01

    Roč. 55, č. S1 (2006), S73-S80 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:VEGA(SK) 2/6139/26 Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneous hypertension * hypertriglyceridemia * vascular reactivity Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  1. Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats

    NARCIS (Netherlands)

    Racasan, S; Braam, B; van der Giezen, DM; Goldschmeding, R; Boer, P; Koomans, HA; Joles, JA

    Embryo cross-transplantation and cross-fostering between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) suggest that perinatal environment modulates the genetically determined phenotype. In SHR the balance between NO and reactive oxygen species (ROS) is disturbed. We hypothesized

  2. Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats

    NARCIS (Netherlands)

    Koeners, Maarten P.; Wesseling, Sebastiaan; Ulu, Arzu; Lopez Sepulveda, Rocio; Morisseau, Christophe; Braam, Branko; Hammock, Bruce D.; Joles, Jaap A.

    Koeners MP, Wesseling S, Ulu A, Sepulveda RL, Morisseau C, Braam B, Hammock BD, Joles JA. Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats. Am J Physiol Endocrinol Metab 300: E691-E698, 2011. First published January 25, 2011; doi:

  3. Differential remodeling of carotid artery in spontaneously hypertensive and hereditary hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Cebová, M.; Kristek, F.; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. S1 (2006), S81-S87 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:VEGA(SK) 2/6139/26 Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneous hypertension * hypertriglyceridemia * conduit artery Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  4. Mechanism of indapamide-induced prevention of spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, O.; Kojšová, S.; Jendeková, L.; Zicha, Josef

    2005-01-01

    Roč. 46, č. 4 (2005), s. 912-912 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] Grant - others:VEGA(SK) 2/3185/24; VEGA(SK) 1/1171/24; VEGA(SK) 1/0540/24; APVT(SK) 51-017902 Keywords : indapamid * hypertension Subject RIV: ED - Physiology

  5. Connexin 50 Mutation Lowers Blood Pressure in Spontaneously Hypertensive Rat

    Czech Academy of Sciences Publication Activity Database

    Šeda, Ondřej; Liška, F.; Pravenec, Michal; Vernerová, Z.; Kazdová, L.; Křenová, D.; Zídek, Václav; Šedová, Lucie; Krupková, M.; Křen, V.

    2017-01-01

    Roč. 66, č. 1 (2017), s. 15-28 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:68378050 ; RVO:67985823 Keywords : Connexin * Hypertension * Transcriptome * Animal models * Insulin resistance Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (FGU-C) Impact factor: 1.461, year: 2016

  6. Combined Effects of Socioeconomic Position, Smoking, and Hypertension on Risk of Ischemic and Hemorrhagic Stroke

    DEFF Research Database (Denmark)

    Nordahl, Helene; Osler, Merete; Frederiksen, Birgitte Lidegaard

    2014-01-01

    BACKGROUND AND PURPOSE: Combined effects of socioeconomic position and well-established risk factors on stroke incidence have not been formally investigated. METHODS: In a pooled cohort study of 68 643 men and women aged 30 to 70 years in Denmark, we examined the combined effect and interaction...... between socioeconomic position (ie, education), smoking, and hypertension on ischemic and hemorrhagic stroke incidence by the use of the additive hazards model. RESULTS: During 14 years of follow-up, 3613 ischemic strokes and 776 hemorrhagic strokes were observed. Current smoking and hypertension were...... more prevalent among those with low education. Low versus high education was associated with greater ischemic, but not hemorrhagic, stroke incidence. The combined effect of low education and current smoking was more than expected by the sum of their separate effects on ischemic stroke incidence...

  7. Tooth loss, hypertension and risk for stroke in a Korean population.

    Science.gov (United States)

    Choe, Heon; Kim, Young Ho; Park, Ji Wan; Kim, Su Young; Lee, Sang-Yi; Jee, Sun Ha

    2009-04-01

    Tooth loss has been suggested as a potential risk factor for stroke. We conducted a prospective cohort study of stroke in Korea on hypertension, diabetes, smoking, and tooth loss to characterize their independent effects and interactions. The overall risk of stroke and the risk of different subtypes of stroke were evaluated in relation to tooth loss using Cox proportional hazards models among 867,256 Korean men and women, aged 30-95 years, who received health insurance from the National Health Insurance Corporation and were medically evaluated between 1992 and 1995, with tooth loss measured. The overall prevalence of having at least one tooth removed among the people in the study was 29.8% (31.9% for men and 22.3% for women). During a 14-year follow-up, 28,258 strokes with 5105 fatal strokes occurred. For men and women, tooth loss was associated with total stroke and stroke subtypes. In a multivariable model adjusting for selected covariates, a graded association between higher tooth loss and higher risk of total stroke was observed in men [> or =7 lost teeth versus 0 (hazard ratio (HR)=1.3; 95% confidence interval (CI), 1.2-1.4)] and in women (HR=1.2; 95% CI, 1.0-1.3). The HRs for ischemic and hemorrhagic stroke were also similar in men and women. There was evidence of interaction of hemorrhagic stroke risk with hypertension and tooth loss. Tooth loss is independently associated with increased risk of stroke and hypertension does interact antagonistically, particularly for hemorrhagic stroke.

  8. Reduced kidney function and outcome in acute ischaemic stroke: relationship to arterial hypertension and diabetes.

    Science.gov (United States)

    Losito, Attilio; Pittavini, Loretta; Ferri, Carla; De Angelis, Luigi

    2012-03-01

    Stroke is a dangerous long-term complication of kidney failure, yet its occurrence early in disease is poorly characterized. Our aim was to investigate the association of reduced kidney function, hypertension and diabetes with acute ischaemic stroke and the outcome thereof. In this prospective cohort study, the association of reduced kidney function, hypertension and diabetes with stroke and 2-year all-cause mortality was investigated. Glomerular filtration rate (eGFR) was estimated by the simplified Modification of Diet in Renal Disease formula in 13 365 consecutive patients (671 with acute ischaemic stroke) admitted to our clinical facility over a 12-month period. Ischaemic stroke, after adjustment for age and gender, was significantly associated with eGFR stroke. Age and gender-adjusted survival analysis by Cox regression showed an association of mortality with reduced eGFR alone (HR = 4.29, 95% CI 1.02-19.60). In patients acutely admitted to hospital, reduced kidney function, hypertension and diabetes are independently associated with ischaemic stroke, but do not exert a synergic effect. After hospital discharge, mortality is strongly associated with reduced eGFR but with neither hypertension nor diabetes.

  9. Association of benign intracranial hypertension and spontaneous encephalocele with cerebrospinal fluid leak.

    Science.gov (United States)

    Brainard, Laura; Chen, Douglas A; Aziz, Khaled M; Hillman, Todd A

    2012-12-01

    To determine the incidence of intracranial hypertension in patients with spontaneous encephalocele with cerebrospinal fluid (CSF) leak. Retrospective case review. Tertiary care neurotology practice. Patients presenting between 2008 and 2011 with spontaneous encephalocele and CSF leak in the temporal bone. Lumbar puncture with opening pressure measurement after encephalocele repair. Patient age, sex, postoperative course, body mass index, and postoperative intracranial pressure. Of the 26 patients identified with spontaneous encephalocele with CSF leak, 9 patients had postoperative lumbar puncture data. Of those 9, 89% were female subjects, and 11% were male, with a mean age of 57 and a mean BMI of 41 kg/m (morbidly obese). The mean opening pressure was 24.5 cm H(2)O. Approximately 33% had normal intracranial pressure (mean, 15 cm H(2)O; range, 10-17 cm H(2)O); 67% had elevated intracranial pressure (mean, 29 cm H(2)O; range, 23.5-40 cm H(2)O). The incidence of BIH in the general population is 0.001%. Of the 6 with intracranial hypertension, 3 (50%) were placed on acetazolamide for fundoscopic findings, postoperative headache, and/or visual changes. Mean time to LP after repair of encephalocele was 13 months (range, 4 days to 75 months). This study shows that benign intracranial hypertension is prevalent in a significant number of patients presenting with spontaneous encephalocele with CSF otorrhea at a rate much higher than is found in the general population. This finding has direct clinical implications and suggests that all patients with spontaneous encephalocele/CSF leak warrant evaluation for benign intracranial hypertension.

  10. Standards and pitfalls of focal ischemia models in spontaneously hypertensive rats: With a systematic review of recent articles

    Directory of Open Access Journals (Sweden)

    Yao Hiroshi

    2012-07-01

    Full Text Available Abstract We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR, and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001–2010, and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress.

  11. Pre-existing hypertension dominates γδT cell reduction in human ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Mateusz G Adamski

    Full Text Available T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors. Peripheral blood samples from 43 acute ischemic stroke patients and 26 control subjects matched on race and gender were used for flow cytometry and complete blood count analyses. Subsequently, cytokine levels and gene expression were measured in γδT cells. The number of circulating γδT cells was decreased by almost 50% (p = 0.005 in the stroke patients. γδT cell counts did not correlate with lesion volume on magnetic resonance diffusion-weighted imaging or with clinical severity in the stroke patients, but γδT cells showed elevated levels of IL-17A (p = 0.048. Decreased γδT cell counts were also associated with older age (p = 0.004, pre-existing hypertension (p = 0.0005 and prevalent coronary artery disease (p = 0.03, with pre-existing hypertension being the most significant predictor of γδT cell counts in a multivariable analysis. γδT cells in human ischemic stroke are reduced in number and show elevated levels of IL-17A. A major reduction in γδT lymphocytes also occurs in hypertension and may contribute to the development of hypertension-mediated stroke and vascular disease.

  12. Vascular reactivity of arteria femoralis in adult and aged spontaneously hypertensive and Wistar-Kyoto rats.

    Science.gov (United States)

    Petrova, M; Liskova, S; Vojtko, R; Villaris, R; Varga, Z; Zicha, J; Kristova, V

    2013-01-01

    The relationship of age and hypertension on endothelial dysfunction and increased responses to vasoconstrictor stimuli. Hypertension is a disease accompanied by endothelial dysfunction and is characterized by an impaired vascular reactivity and enhanced activity of sympathetic nervous system. In our experiment, we used spontaneously hypertensive rats representing model of essential hypertension and the Wistar-Kyoto rats as normotensive strain. Femoral arteries of adult and aged rats were put into the chamber of Mulvany-Halpern isometric myograph. As the nutrient solution, the modified Krebs-Henseleit solution having temperature 37 °C and bubbled with O2 was used. After 30 minutes stabilization of blood vessels, a dose-dependent curve of norepinephrine response was recorded (concentrations 3x10-8 M, 10-7 M, 3x10-7 M, 10-6 M, 3x10-6 M, 10-5 M, 3x10-5 M, 10-4 M), followed by a dose-dependent curve of acetylcholine response (concentrations 3x10-8 M, 10-7 M, 3x10-7 M, 10-6 M, 3x10-6 M). Our experiments recorded an increased reactivity to contraction stimuli in spontaneously hypertensive animals. Vascular reactivity to norepinephrine at 5 month and 12 month old rats from the same group was not significantly affected. Our experiments on the other hand, did not record a reduced endothelium-dependent relaxation in hypertensive compared to normotensive animals, neither in different age groups. Increased norepinephrine-induced contraction occurs even before development of reduced acetylcholine-induced relaxation in SHR rats. We predict that in our experiment hypertension plays a bigger role in the development of endothelial dysfunction than aging (Fig. 2, Ref. 22).

  13. N-Acetylcysteine Prevents Hypertension via Regulation of the ADMA-DDAH Pathway in Young Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Nai-Chia Fan

    2013-01-01

    Full Text Available Asymmetric dimethylarginine (ADMA reduces nitric oxide (NO, thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH, which can be inhibited by oxidative stress. N-Acetylcysteine (NAC, an antioxidant, can facilitate glutathione (GSH synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR. Rats aged 4 weeks were assigned into 3 groups (n=8/group: control Wistar Kyoto rats (WKY, SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway.

  14. Vasopressin and oxytocin gene expression in the supraoptic and paraventricular nucleus of the spontaneously hypertensive rat (SHR) during development of hypertension

    NARCIS (Netherlands)

    Tol, H.H.M. van; Buuse, M. van den; Jong, Wybren de; Burbach, J.P.H.

    1988-01-01

    To study the regulation of hypothalamic vasopressin (VP) and oxytocin (OT) gene expression in relation to the development of hypertension, levels of VP mRNA and OT mRNA were determined in spontaneously hypertensive rats (SHR). Differences in VP and OT mRNA content of the supraoptic nucleus (SON) and

  15. Beta-adrenoceptors in kidney tubules of spontaneously hypertensive and normotensive rats

    International Nuclear Information System (INIS)

    Struyker-Boudier, H.A.J.; Vervoort-Peters, L.H.T.M.; Rousch, M.J.M.; Smits, J.F.M.; Thijssen, H.H.W.

    1986-01-01

    Beta-adrenoceptor binding characteristics were determined in different fractions of rat kidney tubules using a ( 125 Iodo)-(-)-cyanopindolol (ICYP) binding assay. The highest amount of binding sites was found in a fraction containing predominantly distal tubular fragments. In a separate series of experiments the ICYP binding characteristics were compared in whole tubular fractions from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) of different ages. The maximum number of binding sites was significantly higher both in young (3 weeks) and adult (14 weeks) SHR when compared to age-matched WKY. These studies showed the presence of beta-adrenoceptor binding sites in rat kidney tubules and support the potential importance of tubular beta-adrenoceptors in the development of spontaneous hypertension and in the mechanism of antihypertensive action of beta-blockers. 35 references, 1 figure, 3 tables

  16. The relation between knowledge about hypertension and education in hospitalized patients with stroke in Vienna.

    Science.gov (United States)

    Samal, Doris; Greisenegger, Stefan; Auff, Eduard; Lang, Wilfried; Lalouschek, Wolfgang

    2007-04-01

    Knowledge about hypertension and its control influences blood pressure control in patients with hypertension. We assessed these parameters in a large cohort of patients with ischemic stroke or transient ischemic attack and analyzed their association with educational attainment. Five hundred ninety-one consecutive patients with stroke with a medical history of hypertension were interviewed about knowledge concerning hypertension within a multicenter hospital-based stroke registry. We analyzed answers in relation to educational level with multivariate logistic regression adjusted for age and sex. Seventy-seven percent of the patients stated to have known about hypertension being a risk factor for stroke, but only 30% felt at increased risk of stroke. Less than half (47%) could identify 140 mm Hg or less as the maximum tolerated systolic blood pressure, and 53% had their blood pressure only controlled monthly or less often. Knowledge of possible consequences of myocardial infarction, nephropathy, peripheral vascular disease, and retinopathy was 64%, 20%, 11%, and 16%, respectively. Approximately half of patients were acquainted with the nonpharmacologic treatment options of physical activity (49%), reduction of salt intake (54%), and reduction of caloric intake (48%), whereas relaxation techniques were only known to 17%. Adherence to those treatment options ranged from 42% to 67%. Educational level was significantly associated with knowledge of increased risk, possible consequences of hypertension, and knowledge about nonmedication treatment options. Knowledge in our population was insufficient and partly associated with educational level, leaving much room for improvement by educational campaigns. Furthermore, we found a gap between knowledge of the increased risk for stroke in patients with hypertension and awareness of their own risk.

  17. Contribution of captopril thiol group to the prevention of spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga

    2007-01-01

    Roč. 56, Suppl.2 (2007), S41-S48 ISSN 0862-8408 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; APPV(SK) 0586-06 Institutional research plan: CEZ:AV0Z50110509 Keywords : captopril and enalapril * thiols * spontaneous hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

  18. The genome sequence of the spontaneously hypertensive rat: Analysis and functional significance

    Czech Academy of Sciences Publication Activity Database

    Atanur, S. S.; Birol, I.; Guryev, V.; Hirst, M.; Hummel, O.; Morrissey, C.; Behmoaras, J.; Fernandez-Suarez, X.M.; Johnson, M. D.; McLaren, W. M.; Patone, G.; Petretto, E.; Plessy, Ch.; Rockland, K. S.; Rockland, Ch.; Saar, K.; Zhao, Y.; Carninci, P.; Flicek, P.; Kurtz, T.; Cuppen, E.; Pravenec, Michal; Hubner, N.; Jones, S. J. M.; Birney, E.; Aitman, T. J.

    2010-01-01

    Roč. 20, č. 6 (2010), s. 791-803 ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520 Grant - others:EC(XE) LSHG-CT-2005-019015; HHMI(US) HHMI; Transatlantic network of excellence(US) Foundation Leducq Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneously hypertensive rat * genome sequence * genetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 13.588, year: 2010

  19. Effect of Antihypertensive Drug Treatment on Oxidative Stress Markers in Heart of Spontaneously Hypertensive Rat Models.

    Science.gov (United States)

    Yusoff, Nik Syamimi Nik; Mustapha, Zulkarnain; Sharif, Sharifah Emilia Tuan; Govindasamy, Chandran; Sirajudeen, Kuttulebbai Nainamohamed Salam

    2017-01-01

    Oxidative stress has been suggested to play a role in hypertension- and hypertension-induced organ damage. The effect of antihypertensive drug treatments on oxidative stress markers has not been well assessed. Therefore, in this study we investigated the effect of enalapril on oxidative stress markers in hearts of hypertensive rat models such as spontaneously hypertensive rats (SHR) and SHRs administered N-nitro-L-arginine methyl ester (SHR+L-NAME rats). Male rats were divided into four groups: SHRs, SHR+enalapril (SHR-E) rats, SHR+L-NAME rats, SHR+enalapril+L-NAME (SHRE+L-NAME) rats. Rats (SHREs) were administered enalapril (30 mg kg-1 day-1) in drinking water from week 4 to week 28 and L-NAME (25 mg kg-1 day-1) from week 16 to week 28 in drinking water. At the end of 28 weeks, animals were sacrificed, and their hearts were collected for the assessment of oxidative stress markers and histological examination. Enalapril treatment significantly enhanced the total antioxidant status (TAS) (P heart. The fibrosis areas in SHRs and SHR+L-NAME rats were also markedly reduced. These findings suggest that enalapril might play a protective role in hypertension- and hypertension-induced organ damage.

  20. DYSFUNCTIONAL PRESYNAPTIC ALPHA-2-ADRENOCEPTORS EXPOSE FACILITATORY BETA-2-ADRENOCEPTORS IN THE VASCULATURE OF SPONTANEOUSLY HYPERTENSIVE RATS

    NARCIS (Netherlands)

    REMIE, R; VANROSSUM, JXM; COPPES, RP; ZAAGSMA, J

    1992-01-01

    Previous studies on spontaneously hypertensive rats (SHR) have yielded inconsistent information about functional aberrations of the presynaptic alpha(2)- and beta(2)-adrenoceptor-mediated modulation of sympathetic neurotransmitter release. In the present investigation we studied the capacity of

  1. Antihypertensive effect of fermented skim camel (Camelus dromedarius) milk on spontaneously hypertensive rats.

    Science.gov (United States)

    Yahya, Mohammed A; Alhaj, Omar A; Al-Khalifah, Abdullrahman S

    2017-03-30

    Hypertension is one of the most common diseases in worldwide, thus prevention of hypertension is important in reducing the risks of cardiovascular disease. Milk contains bioactive peptides released during milk fermentation which lead to exhibit angiotensin I converting enzyme (ACE) inhibitory. The aim of this study was to investigate the antihypertensive effect of fermented skim camel milk on rats and compared with unfermented skim camel milk as control. The antihypertensive effect of fermented skim camel milk on thirty six male spontaneously hypertensive rats (SHR) was carried out for (short-term) and (long-term) using different doses (80, 240 and 1200 mg/kg body weight). Angiotensin converting enzyme (ACE) activity was also measured using ACE Kit. The blood pressure (systolic and diastolic) of spontaneously hypertensive rats (SHR) in short term administration (24 hours) of 1200 mg/kg body weight fermented skim camel milk decreased significantly (p camel milk for long-term (20 days) decreased and affected the heart rate (beats/min). The lowest record of systolic (41 mmHg) and diastolic blood pressure (19 mmHg) were at dose of 1200 mg/kg body weight of fermented skim camel milk at 15 days of administration. Likewise, ACE activity in plasma of SHR administered fermented skim camel milk decreased significantly (p camel milk by L. helveticus and S. thermophillus in SHR rats depends on the high dose of fermented skim camel milk in short and long-term. The ACE activity inhibitory was clear with fermented skim camel milk.

  2. Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Coan, P. M.; Hummel, O.; Diaz, A. G.; Barrier, M.; Alfazema, N.; Norsworthy, P. J.; Pravenec, Michal; Petretto, E.; Hübner, N.; Aitman, T. J.

    2017-01-01

    Roč. 10, č. 3 (2017), s. 297-306 ISSN 1754-8403 R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : rat * congenic * genomic * hypertension * insulin resistance Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 4.691, year: 2016

  3. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat.

    Directory of Open Access Journals (Sweden)

    Mitsunori Miyazaki

    Full Text Available It is well known that spontaneously hypertensive rats (SHR develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007 linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including Mck, Ttn and Mef2c. We next performed circadian time-course collections at a young age (8 weeks; pre-hypertensive and adult age (22 weeks; hypertensive to determine if clock gene expression was disrupted in gastrocnemius, heart and liver tissues prior to or after the rats became hypertensive. We found that hypertensive/hypertrophic SHR showed a dampening of peak Bmal1 and Rev-erb expression in the liver, and the clock-controlled gene Pgc1α in the gastrocnemius. In addition, the core-clock gene Clock and the muscle-specific, clock-controlled gene Myod1, no longer maintained a circadian pattern of expression in gastrocnemius from the hypertensive SHR. These findings provide a framework to suggest a mechanism whereby chronic heart failure leads to skeletal muscle pathologies; prolonged dysregulation of the molecular clock in skeletal muscle results in altered Clock, Pgc1α and Myod1 expression which in turn leads to the mis-regulation of target genes important for mechanical and metabolic function of skeletal muscle.

  4. Neuroprotective efficacy of subcutaneous insulin-like growth factor-I administration in normotensive and hypertensive rats with an ischemic stroke.

    Science.gov (United States)

    De Geyter, D; Stoop, W; Sarre, S; De Keyser, J; Kooijman, R

    2013-10-10

    The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were investigated in both rat strains using the endothelin-1 rat model for ischemic stroke. Motor-sensory functions were measured using the Neurological Deficit Score. Infarct size was assessed by Cresyl Violet staining. Subcutaneous administration of IGF-I resulted in significantly reduced infarct volumes and an increase in motor-sensory functions in normotensive rats. In these rats, IGF-I did not modulate blood flow in the striatum and had no effect on the activation of astrocytes as assessed by GFAP staining. In hypertensive rats, the protective effects of IGF-I were smaller and not always significant. Furthermore, IGF-I significantly reduced microglial activation in the cortex of hypertensive rats, but not in normotensive rats. More detailed studies are required to find out whether the reduction by IGF-I of microglial activation contributes to an impairment IGF-I treatment efficacy. Indeed, we have shown before that microglia in hypertensive rats have different properties compared to those in control rats, as they exhibit a reduced responsiveness to ischemic stroke and lipopolysaccharide. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Neurogenic pulmonary edema induced by spinal cord injury in spontaneously hypertensive and Dahl salt hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Šedý, Jiří; Kuneš, Jaroslav; Zicha, Josef

    2011-01-01

    Roč. 60, č. 6 (2011), s. 975-979 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/09/0336; GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypertension * neurogenic pulmonary edema * Dahl salt-sensitive rats * SHR Subject RIV: ED - Physiology Impact factor: 1.555, year: 2011

  6. Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke.

    Science.gov (United States)

    Aquilani, Roberto; Scocchi, Marco; Iadarola, Paolo; Franciscone, Piero; Verri, Manuela; Boschi, Federica; Pasini, Evasio; Viglio, Simona

    2008-12-01

    To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke. Alimentation-independent patients with ischaemic stroke were randomly allocated to either 21 days of protein supplementation (protein-supplemented group; n=20) or to a spontaneous diet only (control group; n=21) in order to investigate the recovery of neurological changes (measured using the National Institute of Health (NIH) Stroke Scale). Tertiary care rehabilitation in Italy. Forty-two patients (27 male and 15 female; 66.4 +/- 11 years) 16 +/-2 days after the acute event. Supplementation with a hyperproteic nutritional formula (10% protein). NIH Stroke Scale and protein intake. At admission to rehabilitation, both groups of patients were homogeneous for demographic, clinical and functional characteristics. After 21 days from the start of the protocol, the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins (-4.4 +/- 1.5 score versus -3 +/- 1.4 of control group; Pneurological recovery in subacute patients with ischaemic stroke.

  7. Heart and Stroke Foundation of Ontario (HSFO) high blood pressure strategy's hypertension management initiative study protocol

    OpenAIRE

    Tobe, Sheldon W; Lum-Kwong, Margaret Moy; Perkins, Nancy; Von Sychowski, Shirley; Sebaldt, Rolf J; Kiss, Alex

    2008-01-01

    Abstract Background Achieving control of hypertension prevents target organ damage at both the micro and macrovascular level and is a highly cost effective means of lowering the risk for heart attack and stroke particularly in people with diabetes. Clinical trials demonstrate that blood pressure control can be achieved in a large proportion of people. Translating this knowledge into widespread practice is the focus of the Hypertension Management Initiative, which began in 2004 with the goal o...

  8. Chronic changes of hematocrit value alter blood pressure and glomerular filtration in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Milanović S.

    2012-01-01

    Full Text Available Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR. Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite - lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.

  9. Hepatoprotective Effect of Silymarin (Silybum marianum on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Abel Felipe Freitag

    2015-01-01

    Full Text Available This study was aimed to investigate the effect of Silymarin (SLM on the hypertension state and the liver function changes induced by acetaminophen (APAP in spontaneously hypertensive rat (SHR. Animals normotensive (N or hypertensive (SHR were treated or not with APAP (3 g/kg, oral or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT, aspartate aminotransferase (AST, glucose (GLU, gamma glutamyl transferase (γ-GT, and alkaline phosphatase (ALP of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO activity and nitric oxide (NO production and were also sectioned for histological analysis. No differences were observed for ALT, γ-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, γ-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals.

  10. Combined antihypertensive effect of luteolin and buddleoside enriched extracts in spontaneously hypertensive rats.

    Science.gov (United States)

    Lv, Gui-Yuan; Zhang, Yan-Ping; Gao, Jian-Li; Yu, Jing-Jing; Lei, Jing; Zhang, Zhi-Ru; Li, Bo; Zhan, Ruan-Juan; Chen, Su-Hong

    2013-11-25

    Flos Chrysanthemi is used in a variety of diseases in traditional Chinese medicine including hypertension, and the total flavonoids (rich in luteolin (LUT) and buddleoside (BUD)) of Flos Chrysanthemi is known to modulate vascular functions and reduce the blood pressure. However, the active flavonoids and their synergistic effects on anti-hypertension are still unclear. To investigate the combined anti-hypertension effects of LUT and BUD enriched extracts on spontaneously hypertensive rats (SHR), as well as the anti-hypertensive mechanism of LUT&BUD mixture. CODA Mouse & Rat Tail-Cuff Blood Pressure System was used to measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR after treated with extracts contains with LUT and/or BUD. The expressions of Ang II, PRA, ALD, ET, PGI2 and TXB2 were investigated by ELASA. Serum NO concentration was measured by the method of Nitric acid reductase. A single administration of LUT, BUD, or LUT:BUD=1:1 significantly reduced SBP by about 3.35 mmHg, 4.39 mmHg and 15.42 mmHg, respectively. Chronic administration of LBM (at 60 mg/kg; p.o. for 30 days) reduced both SBP and DBP by 4.04% and 5.24% of the vehicle group, respectively. Oral administration of LBM at 60 mg/kg inhibited the serum levels of ANG, ALD and ET, but increased serum NO concentration. This study shows the synergistic anti-hypertension effects of LUT and BUD in SHR. The effects of LBM on blood pressure are associated with RAAS and endothelial system. Thus, our experiments suggest that the combination of luteolin and buddleoside from Flos Chrysanthemi are potentially useful for the therapeutic treatments for hypertension. © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Zicha, Josef; Paulis, Ĺudovít; Zenebe, W.; Dobešová, Zdenka; Kojšová, S.; Jendeková, L.; Sládková, M.; Dovinová, I.; Šimko, F.; Kuneš, Jaroslav

    2007-01-01

    Roč. 561, 1-3 (2007), s. 129-136 ISSN 0014-2999 R&D Projects: GA MZd(CZ) NR7786; GA ČR GA305/03/0769 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; VEGA(SK) 1/3442/26; APVT(SK) 51-027404; APVT(SK) 51-017902 Institutional research plan: CEZ:AV0Z5011922 Keywords : NO synthase * oxidative load * genetic hypertension Subject RIV: ED - Physiology Impact factor: 2.376, year: 2007

  12. Longitudinal prevalence of hypertension, proteinuria, and retinopathy in dogs with spontaneous diabetes mellitus.

    Science.gov (United States)

    Herring, I P; Panciera, D L; Werre, S R

    2014-01-01

    The prevalence and progression of vascular complications of spontaneous diabetes mellitus (DM) in dogs have not been described. To investigate the effects of duration of disease, as estimated by time since DM diagnosis, and glycemic control on prevalence of systemic hypertension, proteinuria, and diabetic retinopathy in dogs with spontaneous DM. Seventeen client-owned dogs with spontaneous DM. Prospective, longitudinal observational study. Dogs with DM of less than 1 year's duration were recruited and evaluated once every 6 months for 24 months. Recorded measures included indirect BP, urine albumin, protein and creatinine concentrations, serial blood glucose and serum fructosamine concentrations, ophthalmic examination, and a standardized behavioral questionnaire. Eleven dogs completed the 2-year follow-up period, during which the highest recorded prevalence of systolic and diastolic hypertension was 55 and 64%, respectively. Prevalence of microalbuminuria and elevated urine protein:creatinine ratio (UPC) ranged up to 73 and 55%, respectively. Prevalence of retinopathy ranged up to 20%. No significant effect of time since DM diagnosis or glycemic control was detected for any of the measures examined. Additionally, no significant associations between BP, urine albumin concentration, UPC and retinopathy were detected. With the exception of proteinuria, which was substantial in some cases, clinically deleterious diabetic vascular complications were not identified in dogs in this study. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  13. Vitamin D, Hypertension, and Ischemic Stroke in 116 655 Individuals From the General Population

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Nordestgaard, Børge G

    2017-01-01

    Observational studies indicate that low concentrations of plasma 25-hydroxyvitamin D (25(OH)D) are associated with high blood pressure, hypertension, and ischemic stroke. However, whether these associations are causal remain unknown. A total of 116 655 white individuals of Danish descent from...

  14. H-Type Hypertension and C Reactive Protein in Recurrence of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Qing Zhang

    2016-05-01

    Full Text Available Hypertension with high homocysteine (HHcy (H-type hypertension and C reactive protein (CRP can increase the incidence of ischemic stroke. However, it is not clear whether recurrent ischemic stroke (RIS is related to H-type hypertension and CRP. The present study investigated the correlation of H-type hypertension and CRP level with RIS. Totally, 987 consecutive patients with acute ischemic stroke were recruited in a teaching hospital in Henan province, China during March 2014 to March 2015. The demographic and clinical characteristics and blood biochemical parameters of patients were analyzed. Elevated levels of CRP and homocysteine (Hcy were defined as >8.2 mg/L and 10 μmol/L, respectively. Among the 987 patients, 234 were RIS. Thirty-eight percent of RIS patients had elevated CRP level and 91.5% of RIS patients had HHcy. In multivariate analysis, adjusted odds ratio (OR of RIS in patients aged ≥60 years was 1.576 (95% CI: 1.125–2.207, in male patients 1.935 (95% CI: 1.385–2.704, in patients with diabetes 1.463 (95% CI: 1.037–2.064, CRP levels 1.013 (95% CI: 1.006–1.019, simple hypertension 3.370 (95% CI: 1.15–10.183, and H-type hypertension 2.990 (95% CI: 1.176–7.600. RIS was associated with older age, male, diabetes, H-type hypertension and CRP. Controlling H-type hypertension and CRP level may reduce the risk of RIS.

  15. The effects of supraphysiological supplementation of b-carotene in spontaneously hypertensive rats (SHR and SHR-sp

    Directory of Open Access Journals (Sweden)

    Stênio Karlos Alvim Fiorelli

    Full Text Available Objective: to investigate the effect of administration of supraphysiological âcaroteno on biological parameters (ectoscopy and blood pressure, laboratory (malondialdehyde and histological (liver and carotid arteries of spontaneously hypertensive rats prone to stroke (SHR-sp.Methods: we used 36 male rats were divided into three groups, each containing 12 rats Wistar, SHR and SHR-sp, subdivided into six control animals and six animals treated with supraphysiological doses of âcaroteno for two periods of ten weeks interspersed with one week interruption. In the experiment were assessed daily physical examination and blood pressure (plethysmography. At sacrifice, blood was collected for measurement of serum malondialdehyde, liver and carotid arteries for histological examination.Results: temporary change in color of the fur, decreased significantly (p<0.0001 blood pressure (20mg supplementation âcaroteno and serum levels of malondialdehyde (p<0.05 and increased amount of elastic fibers in the carotid wall of SHR and SHR-sp.Conclusion: supplementation of supraphysiological âcaroteno caused no toxic effects, showed positive response in the modulation of blood pressure and lower serum malondialdehyde. No significant morphological changes were found in both groups, except an increase in the number of elastic fibers in the muscle layer carotid suggesting elastosis in SHR and SHR-sp.

  16. Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

    Science.gov (United States)

    Attakpa, E S; Bertin, G A; Chabi, N W; Ategbo, J-M; Seri, B; Khan, N A

    2017-11-24

    Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

  17. Egg-derived tri-peptide IRW exerts antihypertensive effects in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Kaustav Majumder

    Full Text Available There is a growing interest in using functional food components as therapy for cardiovascular diseases such as hypertension. We have previously characterized a tri-peptide IRW (Ile-Arg-Trp from egg white protein ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and angiotensin converting enzyme (ACE inhibitor properties in vitro. Given the pathogenic roles played by angiotensin, oxidative stress and inflammation in the spontaneously hypertensive rat (SHR, we tested the therapeutic potential of IRW in this well-established model of hypertension.16-17 week old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW or a high dose (15 mg/Kg BW daily for 18 days. Blood pressure (BP and heart rate were measured by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and measuring markers of inflammation. IRW treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose groups respectively compared to untreated SHRs. Heart rate was not affected. Reduction in BP was accompanied by the restoration of diurnal variations in BP, preservation of nitric oxide dependent vasorelaxation, as well as reduction of plasma angiotensin II, other inflammatory markers and tissue fibrosis.Our results demonstrate anti-hypertensive effects of IRW in vivo likely mediated through ACE inhibition, endothelial nitric oxide synthase and anti-inflammatory properties.

  18. Antihypertensive and antioxidant effects of supplementation with red wine pomace in spontaneously hypertensive rats.

    Science.gov (United States)

    Del Pino-García, Raquel; Rivero-Pérez, María D; González-SanJosé, María L; Croft, Kevin D; Muñiz, Pilar

    2017-07-19

    Hypertension is associated with enhanced vascular oxidative stress and impaired endothelial function, which is related to an imbalance between reactive oxygen species and nitric oxide bioavailability. Short-term supplementation with a polyphenol-rich powdered red wine pomace seasoning (RWPS) was investigated for its effects on blood pressure and biomarkers of endothelial dysfunction and oxidative status in a model of essential hypertension. Male spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (12-week-old, 5 rats per group) were administered RWPS (300 mg kg -1 day -1 ; equivalent to 7.32 mg gallic acid per kg per day) or vehicle by gavage. In SHRs, 4-week RWPS supplementation progressively decreased blood pressure, reaching 11.5% reduction at the end of the study (p < 0.001). RWPS consumption also increased the ferric reducing ability of plasma and attenuated the oxidation of plasma lipids and proteins, as evidenced by F 2 -isoprostanes, malondialdehyde and protein carbonyl groups as oxidative stress biomarkers. Moreover, nitric oxide production (indirectly measured) was 1.5-fold higher in SHRs + RWPS than that in SHRs (p < 0.05). These beneficial effects were partly attributed to the ability of RWPS-derived bioactive compounds to modulate aortic gene expression, with eNOS, SOD2 and HO-1 over-expression, ACE down-regulation, and no changes in NOX4. In conclusion, this study suggests the potential of red wine pomace-derived seasonings to help in the management of hypertension.

  19. Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus.

    Science.gov (United States)

    Kusaka-Nakamura, M; Kishi, K; Miyazawa, A; Yagi, S; Sokabe, H

    1988-01-01

    Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.

  20. Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Jansa, Petr; Kostka, Vlastimil; Zídek, Václav; Křen, Vladimír; Forejt, Jiří; Kurtz, T. W.

    2001-01-01

    Roč. 12, č. 4 (2001), s. 295-298 ISSN 0938-8990 R&D Projects: GA ČR(CZ) GA305/00/1646; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : mutations in genes * ADD1/SREBP-1c * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.318, year: 2001

  1. Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Šimáková, Miroslava; Křen, Vladimír; Křenová, D.; Horký, K.; Jáchymová, M.; Míková, B.; Kazdová, L.; Aitman, T. J.; Churchill, P. C.; Webb, R. C.; Hingarh, N. H.; Yang, Y.; Wang, J. M.; St.Lezin, E. M.; Kurtz, W. T.

    1999-01-01

    Roč. 103, č. 12 (1999), s. 1651-1657 ISSN 0021-9738 R&D Projects: GA ČR GA306/97/0521; GA ČR GV204/98/K015 Grant - others:NIH(US) ROI HL-56028; NIH(US) PO1 HL-35018; NIH(US) HL-18575 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 * cardiovascular risk factors * spontaneous hypertension Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.921, year: 1999

  2. Hypotensive effect of Chamaemelum nobile aqueous extract in spontaneously hypertensive rats.

    Science.gov (United States)

    Zeggwagh, Naoufel Ali; Moufid, Abderahman; Michel, Jean Baptiste; Eddouks, Mohamed

    2009-07-01

    This study aims to evaluate the hypotensive effect of Chamaemelum nobile aqueous extract (CNAE) in spontaneously hypertensive rats (SHRs). Single oral administration of CNAE (140 mg/kg) produced a significant reduction (p < 0.05) in systolic blood pressure (SBP) after 24 h of the administration. Daily oral administration of CNAE (140 mg/kg) during 3 weeks produced a significant reduction in SBP in the day 8 (p < 0.01) of treatment. Furthermore, CNAE produced a significant increase in urinary output and electrolytes excretion (p < 0.01) from the day 8 to the end of treatment. We conclude that CNAE possesses a hypotensive and diuretic effect in SHR.

  3. Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H

    1989-01-01

    ) and stop-flow pressures (40.0-42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY......Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8-14.7 mm Hg...

  4. Role of the collecting duct in the exaggerated natriuresis of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Francisco, L.L.; DiBona, G.F.

    1980-01-01

    To carry out a comparative examination of exaggerated natriumresis in the kidneys with essential hypertonia, 2 rat populations consisting of 11 spontaneously hypertensive rats (SHR) and, for controlling, 9 Wistar Kyoto rats (WKY), were chosen. In rats of the same age and weight, there was a significant arterial difference in the blood pressure. After the intravenous administration of isotonic NaCl, the urinary flow rate and sodium excretion are increased. The end-distal tubule-microinjection showed the 14 C-inulin recovery while that of 22 Na was significantly higher in SHR than in WKY. (APR) [de

  5. Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats

    OpenAIRE

    Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

    2014-01-01

    OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹), arotinolol (30 mg·kg-1·d⁻¹) for 8 weeks. Ce...

  6. Proximal-tubule-like epithelium in Bowman's capsule in spontaneously hypertensive rats. Changes with age.

    OpenAIRE

    Haensly, W. E.; Granger, H. J.; Morris, A. C.; Cioffe, C.

    1982-01-01

    Kidneys were samples from male spontaneously hypertensive rats (SHR) and normotensive rats (WKY) in four groups. Renal tissues were examined in 64 rats: 6 SHR and 6 WKY rats 8 and 16 weeks of age and 10 SHR and 10 WKY rats 32 and 64 weeks of age. Tissue samples were fixed, processed, and stained by routine histologic procedures. The parietal layer of Bowman's capsule in 100-115 renal corpuscles from right to left kidney sections was classified as squamous or cuboidal epithelium. The cuboidal ...

  7. Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Jansa, Petr; Kostka, Vlastimil; Zídek, Václav; Křen, Vladimír; Forejt, Jiří; Kurtz, W. T.

    2001-01-01

    Roč. 12, č. 4 (2001), s. 295-298 ISSN 0938-8990 R&D Projects: GA ČR GA305/00/1646; GA ČR GV204/98/K015; GA MŠk LN00A079 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922; CEZ:AV0Z5052915 Keywords : mutations in genes * ADD1/SREBP-1c * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.318, year: 2001

  8. Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats

    OpenAIRE

    Moura,José Ricardo Sousa Ayres de; Sass,Nelson; Guimarães,Sérgio Botelho; Vasconcelos,Paulo Roberto Leitão de; Mattar,Rosiane; Kulay Jr,Luis

    2006-01-01

    PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR). METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1). Pregnancy was confirmed by sperm-positive vaginal smear (Day 0). Wistar-EPM-1 rats served as counterpart control (C-1). SHR rats were randomized in 4 groups (n=10): Group Control 2, non-treated rats; Group L-Arginine...

  9. l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats

    OpenAIRE

    Lee, Chee-Wan; Li, Dan; Channon, Keith M.; Paterson, David J.

    2009-01-01

    Spontaneously hypertensive rats (SHR) are known to have cardiac noradrenergic hyperactivity due to an impaired nitric oxide (NO)?cGMP pathway. We hypothesized that dietary l-arginine supplementation may correct this autonomic phenotype. Male SHR and Wistar Kyoto rats (WKY) aged 16?18?weeks were given l-arginine (10?g/L in drinking water) for 1?week. Separate control groups received no supplementation. The SHR control had a significantly lower plasma l-arginine than WKY control, but this was i...

  10. Natriuretic peptide receptor-C attenuates hypertension in spontaneously hypertensive rats: role of nitroxidative stress and Gi proteins.

    Science.gov (United States)

    Li, Yuan; Sarkar, Oli; Brochu, Michèle; Anand-Srivastava, Madhu B

    2014-04-01

    C-Atrial natriuretic peptide (ANP)4-23, a ring deleted analog of ANP that specifically interacts with natriuretic peptide receptor-C (NPR-C), has been shown to decrease the enhanced expression of Giα proteins implicated in the pathogenesis of hypertension. In the present study, we investigated whether in vivo treatment of spontaneously hypertensive rats (SHRs) with C-ANP4-23 could attenuate the development of high blood pressure (BP) and explored the underlying mechanisms responsible for this response. Intraperitoneal injection of C-ANP4-23 at the concentration of 2 or 10 nmol/kg body weight to prehypertensive SHRs attenuated the development of high BP, and at 8 weeks it was decreased by ≈20 and 50 mm Hg, respectively; however, this treatment did not affect BP in Wistar-Kyoto rats. C-ANP4-23 treatment of adult SHRs for 2 weeks also attenuated high BP, heart rate, and restored the impaired vasorelaxation toward control levels. In addition, the enhanced levels of superoxide anion (O2(-)), peroxynitrite, NADPH oxidase activity, and the enhanced expression of Giα proteins, NOX4, p47(phox), nitrotyrosine, and decreased levels of endothelial nitric oxide synthase (eNOS or NOS3) and NO in SHRs were attenuated by C-ANP4-23 treatment; however, the altered levels of NPR-A/NPR-C were not affected by this treatment. In conclusion, these results indicate that NPR-C activation by C-ANP4-23 attenuates the development of high BP in SHRs through the inhibition of enhanced levels of Giα proteins and nitroxidative stress and not through eNOS/cGMP pathway and suggest that NPR-C ligand may have the potential to be used as therapeutic agent in the treatment of cardiovascular complications including hypertension.

  11. Hypertension.

    Science.gov (United States)

    Winter, Katherine H; Tuttle, Laura A; Viera, Anthony J

    2013-03-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease. Antihypertensive treatment substantially reduces the risk of heart failure, stroke, and myocardial infarction. Current guidelines recommend screening all adults for high blood pressure (BP). Lifestyle modifications to help control high BP include weight loss, exercise, moderation of alcohol intake, and a diet low in sodium and saturated fats and high in fruits and vegetables. Out-of-office BP monitoring should be used to confirm suspected white coat effect, especially in patients with apparent resistant hypertension. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Increased risk of stroke in hypertensive women using hormone therapy: analyses based on the Danish Nurse Study

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Jovanovic, Zorana; Heitmann, Berit L

    2003-01-01

    BACKGROUND: Recent randomized clinical trials suggest an increased risk of stroke with hormone therapy (HT), whereas observational studies have suggested mixed results. Differences in design, definitions of HT exposure, and stroke outcome may explain these discrepancies. Little attention has been.......0% of the 13 122 were current HT users, 14.3% were past users, and 57.7% were never users. Overall, HT exposure was not consistently associated with stroke. However, subdivision based on the presence of hypertension showed a significantly increased risk of stroke among hypertensive women. Compared...... with hypertensive never HT users, an increased risk of total stroke was found with current use (hazard ratio, 2.35; 95% confidence interval, 1.16-4.74) and especially with current use of estrogen-progestin (hazard ratio, 3.00; 95% confidence interval, 1.33-6.76). Normotensive women had no increased risk of stroke...

  13. Ambulatory blood pressure monitoring in essential hypertensive patients with acute ischaemic stroke

    Directory of Open Access Journals (Sweden)

    S. P. Zhemanyuk

    2016-12-01

    Full Text Available Blood pressure (BP has been identified as a risk factor for various health disorders, including stroke onsets. Hypertension is one of the crucial health problem among adult Ukrainian. Due to the importance of elevated BP in stroke causality, BP measurement remains critical. However, it is limited information about value in clinical practice of ambulatory blood pressure monitoring (ABPM data in hypertensive patients with inadequately controlled BP with acute stroke compared with those individuals who has no vascular onset. The aim of the study was to determine ABPM parameters in essential hypertensive patients with ischaemic hemisphere stroke. Materials and methods. A total of 114 study participants were analyzed (mean age 62 (56;72 years, 40 % women. We divided them into two groups according to the level of 24-h systolic BP (SBP and diastolic BP (DBP, and the results of clinical examination. The first group (n=83 were inadequately controlled essential hypertensive individuals with high systolic or/and diastolic BP level according to the ABMP results, and the second one (n=31 were EH patients with an acute hemispheric ischaemic stroke (IS. Diagnosis of stroke was confirmed with clinical examination and computed tomography scan or magnetic resonance imaging results, and ABPM was conducted in 4.2±2.3 days after the stroke onset. Results. We had statistician difference (p<0.001 between groups of such parameters, as average SBP (diurnal, daytime, nighttime; diurnal pulse BP; SBP load (p<0.05; the diurnal AASI (p<0.05; circadian rhythm of DBP (p<0.05. No differences were found between the groups in morning surge calculated as speed and amplitude of the BP climbed in morning hours both for SBP (P=0.422 and P=0.395, respectively and DBP (P=0.860 and P=0.337, respectively. Conclusion. In the present study, we evaluated the ABPM parameters in inadequately controlled essential hypertensive individuals with and without acute ischaemic hemispheric stroke

  14. Swimming training prevents coronary endothelial dysfunction in ovariectomized spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    E.R.G. Claudio

    Full Text Available Estrogen deficiency and hypertension are considered major risk factors for the development of coronary heart disease. On the other hand, exercise training is considered an effective form to prevent and treat cardiovascular diseases. However, the effects of swimming training (SW on coronary vascular reactivity in female ovariectomized hypertensive rats are not known. We aimed to evaluate the effects of SW on endothelium-dependent coronary vasodilation in ovariectomized hypertensive rats. Three-month old spontaneously hypertensive rats (SHR, n=50 were divided into four groups: sham (SH, sham plus swimming training (SSW, ovariectomized (OVX, and ovariectomized plus swimming training (OSW. The SW protocol (5 times/week, 60 min/day was conducted for 8 weeks. The vasodilatory response was measured in isolated hearts in the absence and presence of a nitric oxide synthase inhibitor (L-NAME, 100 µM. Cardiac oxidative stress was evaluated in situ by dihydroethidium fluorescence, while the expression of antioxidant enzymes (SOD-2 and catalase and their activities were assessed by western blotting and spectrophotometry, respectively. Vasodilation in SHR was significantly reduced by OVX, even in the presence of L-NAME, in conjunction with an increased oxidative stress. These effects were prevented by SW, and were associated with a decrease in oxidative stress. Superoxide dismutase 2 (SOD-2 and catalase expression increased only in the OSW group. However, no significant difference was found in the activity of these enzymes. In conclusion, SW prevented the endothelial dysfunction in the coronary bed of ovariectomized SHR associated with an increase in the expression of antioxidant enzymes, and therefore may prevent coronary heart disease in hypertensive postmenopausal women.

  15. Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

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    Marcelo D.M. Cezar

    2013-11-01

    Full Text Available Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR. Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72 or spironolactone (SHR-SPR, 20 mg/kg/day, n=34 for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer. Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004. Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg. Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

  16. Amaranth Protein Hydrolysates Efficiently Reduce Systolic Blood Pressure in Spontaneously Hypertensive Rats

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    Giovanni Ramírez-Torres

    2017-11-01

    Full Text Available Alcalase is the enzyme of choice to release antihypertensive peptides from amaranth proteins, but the hydrolysis conditions have not been optimized yet. Furthermore, in vivo assays are needed to confirm such a hypotensive effect. Our aim was to optimize the hydrolysis of amaranth protein with alcalase and to test in vivo the hypotensive effect of the hydrolysates. A response surface analysis was carried out to optimize the hydrolysis reaction. The response variable was the Angiotensin Converting Enzyme (ACE-I inhibition. The hydrolysis degree was determined (free alpha-amino groups measurement. The optimized hydrolysate bioavailability was assessed in the sera of mice and the hypotensive effect was assessed in spontaneously hypertensive rats. Control groups were administered captopril or water. The optimized hydrolysis conditions were: pH = 7.01, temperature = 52 °C, enzyme concentration 0.04 mU/mg, and time = 6.16 h. The optimized hydrolysate showed a 93.5% of ACE-I inhibition and a hydrolysis degree of 74.77%. After supplementation, the hydrolysate was bioavailable in mice from 5 to 60 min, and the hypotensive effect started at 4 h in spontaneously hypertensive rats (p < 0.05 vs. water group. This effect was similar to the captopril hypotensive effect for the next 3 h (p > 0.05. The use of amaranth-optimized hydrolysates as hypotensive supplements or ingredient for functional foods seems feasible.

  17. Pharmacokinetic-pharmacodynamic model of the antihypertensive interaction between telmisartan and hydrochlorothiazide in spontaneously hypertensive rats.

    Science.gov (United States)

    Hao, Kun; Chen, Yuancheng; Zhao, Xiaoping; Liu, Xiaoquan

    2014-08-01

    The goal of this study was to establish an integrated indirect response pharmacokinetic-pharmacodynamic model between telmisartan and hydrochlorothiazide to describe the antihypertensive interaction of these two drugs in spontaneously hypertensive rats. The blood pressure and plasma concentrations were measured by the tail-cuff test and high performance liquid chromatography-mass spectrometry, respectively, in spontaneously hypertensive rats. The current pharmacokinetic-pharmacodynamic model was based on the non-competitive pharmacodynamic interaction of two drugs acting on different physiological processes. This model was able to acquire the temporal changes in drug concentration and blood pressure after administration of telmisartan or hydrochlorothiazide. The noncompetitive pharmacodynamic interaction assumed that the decreased blood pressure was attributed to the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after administration of these two drugs. There was no significant pharmacokinetic change of telmisartan and hydrochlorothiazide in the different groups tested. The model predicted a synergistic pharmacodynamic interaction when telmisartan was administered in combination with hydrochlorothiazide, which was notably stronger than if the effects were additive. The results showed that the presented pharmacokinetic-pharmacodynamic model was suitable for describing the antihypertensive interaction between telmisartan and hydrochlorothiazide. © 2014 Royal Pharmaceutical Society.

  18. Spontaneous coronary thrombosis following thrombolytic therapy for acute cardiovascular accident and stroke: a case study.

    Science.gov (United States)

    Wallace, Eric L; Smyth, Susan S

    2012-11-01

    Cardiac complications following stroke or acute cerebrovascular accidents (CVA) are common; however, many of these complications are asymptomatic and do not cause adverse cardiac effects. Symptomatic events (such as acute myocardial infarction after CVA) rarely occur and are often the result of an underlying cardiac embolic source, such as a left ventricular thrombus. We report a case of spontaneous coronary thrombosis following thrombolytic therapy for acute CVA, and discuss the implication that an underlying systemic pro-thrombotic state may predispose individuals to thrombosis in disparate vascular beds.

  19. Spontaneously hypertensive rats have more orexin neurons in their medial hypothalamus than normotensive rats.

    Science.gov (United States)

    Clifford, Liam; Dampney, Bruno W; Carrive, Pascal

    2015-04-01

    What is the central question of this study? Blockade of orexin receptors reduces blood pressure in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar-Kyoto (WKY) rats, suggesting that upregulation of orexin signalling underlies the hypertensive phenotype of the SHR. However, it is not known what causes this upregulation. What is the main finding and its importance? Using orexin immunolabelling, we show that SHRs have 20% more orexin neurons than normotensive WKY and Wistar rats in the medial hypothalamus, which is a good match to their blood pressure phenotype. In contrast, there is no such match for the orexin neurons of the lateral hypothalamus. Essential hypertension may be linked to an increase in orexin neurons in the medial hypothalamus. The neuropeptide orexin contributes to the regulation of blood pressure as part of its role in the control of arousal during wakefulness and motivated behaviour (including responses to psychological stress). Recent work shows that pharmacological blockade of orexin receptors reduces blood pressure in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar-Kyoto (WKY) rats. It is not clear why orexin signalling is upregulated in the SHR, but one possibility is that these animals have more orexin neurons than their normotensive WKY and Wistar relatives. To test this possibility, SHRs, WKY and Wistar male rats (6-16 weeks old) were killed, perfused and their brains sectioned and immunolabelled for orexin A. Labelled neurons were plotted and counted in the six best labelled hemisections (120 μm apart) of each brain. There were significantly more orexin neurons (+20%) in the medial hypothalamus (medial to fornix) of SHRs compared with WKY and Wistar rats (126 ± 4 versus 106 ± 5 and 104 ± 5 per hemisection, respectively, P hypothalamus did not match the blood pressure phenotypes (69 ± 2 versus 50 ± 3 and 76 ± 4, respectively). The results support the idea that orexin signalling is upregulated

  20. Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

    Science.gov (United States)

    Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

    2014-01-01

    Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+ dep) compared with Na+-independent (Na+ indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na+ indep transport in SHR compared with WKY rats. Total and Na+ dep component of transport were increased, but Na+ indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+ indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced

  1. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    International Nuclear Information System (INIS)

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-01

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of [ 125 I]-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of [ 3 H]-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet

  2. Serial assessment of myocardial thallium perfusion and fatty acid utilization in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sago, Masayoshi; Nishimura, Tsunehiko

    1989-01-01

    To evaluate the advantage of free fatty acid imaging on the detection of hypertrophied myocardium, we compared sequentially myocardial thallium and BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) distribution in spontaneously hypertensive rat (SHR) using dual tracer autoradiography and in vivo pin-hole imaging. Autoradiography and pin-hole imaging showed uniform myocardial distribution of BMIPP and thallium within less than 27 weeks age SHR. In 40 weeks age SHR, thallium myocardial distribution showed uniform, however, BMIPP had focal decrease. Quantitative analysis of pin-hole images showed that myocardial BMIPP and thallium uptake ratio decreased according to the ages of SHR. Our data suggest that hypertension is associated with uniform myocardial perfusion and focal alternation in the substrate used for the performance of myocardial work. Based on the above autoradiographic and in vivo pin-hole imagings, I-123 BMIPP imaging may have a potential for early detection on hypertrophic myocardium compared to thallium perfusion in clinically hypertensive patients. (author)

  3. Moringa oleifera Seeds Attenuate Vascular Oxidative and Nitrosative Stresses in Spontaneously Hypertensive Rats

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    Joseph Iharinjaka Randriamboavonjy

    2017-01-01

    Full Text Available Moringa oleifera (MOI is a tree currently used in traditional medicine in tropical Africa, America, and Asia for therapeutic applications in several disorders including arterial hypertension. We previously described a cardiac protective role of a treatment with MOI seeds in spontaneously hypertensive rats (SHR. Here, we investigated the effects of this treatment on oxidative and nitrosative vascular stresses in SHR, with normotensive Wistar Kyoto rats used as controls. Oxidative and nitrosative stresses detected in SHR aortas using the fluorescent dye dihydroethidine and protein nitrotyrosine staining were reduced in MOI-treated SHR aortas. This was associated with a decrease of free 8-isoprostane circulating level, vascular p22phox and p47phox expressions, and SOD2 upregulation. Moreover, circulating nitrites and C-reactive protein, increased in SHR, were both reduced in SHR receiving MOI. This was associated to decrease iNOS and NF-κB protein expressions after MOI treatment. In functional studies, the endothelium-dependent carbachol-induced relaxation was improved in MOI-treated SHR resistance arteries. Oral administration of MOI seeds demonstrates vascular antioxidant, anti-inflammatory, and endothelial protective effects in SHR. Our data support the use of MOI seeds in diet against cardiovascular disorders associated with oxidative stress and inflammation such as hypertension, scientifically validating the use of these seeds in Malagasy traditional medicine.

  4. MicroRNA Profiling Response to Acupuncture Therapy in Spontaneously Hypertensive Rats

    Science.gov (United States)

    Wang, Jia-You; Li, Hui; Ma, Chun-Mei; Wang, Jia-Lu; Lai, Xin-Sheng; Zhou, Shu-Feng

    2015-01-01

    MicroRNAs (miRNAs) are a group of endogenous noncoding RNAs that play important roles in many biological processes. This study aimed to check if miRNAs were involved in the response to acupuncture in rats. Microarray analysis was performed to compare the miRNA expression profiles of medulla in spontaneously hypertensive rats (SHRs) treated with or without acupuncture. Our microarray analysis identified 222 differentially expressed miRNAs in the medulla of SHRs treated with acupuncture at taichong acupoint. Among these miRNAs, 23 miRNAs with a significant difference were found in acupuncture-treated SHRs compared to untreated rats. These 23 miRNAs could regulate 2963 target genes which were enriched in at least 14 pathways based on our bioinformatic analysis. miRNA-339, miR-223, and miR-145 were downregulated in the medulla of SHRs compared to normotensive rats. Notably, these miRNAs were upregulated to basal levels in the medulla of SHRs treated with acupuncture at taichong in comparison with SHRs receiving acupuncture at nonacupoint group or SHRs without any treatment. Our findings have revealed significant changes of a panel of selective miRNAs in hypertensive rats treated at taichong acupoint. These data provide insights into how acupuncture elicits beneficial effects on hypertension. PMID:25861353

  5. Correlation between homocysteine and dyslipidemia in ischaemic stroke patients with and without hypertension

    Science.gov (United States)

    Aria Arina, Cut; Amir, Darwin; Siregar, Yahwardiah; Sembiring, Rosita J.

    2018-03-01

    Almost 80% of strokes are ischaemic and stroke is the third most common cause of death in developed countries, . The treatment of stroke still limited, the best approach to reduce mortality and morbidity is primary prevention through modification of acquired risk factors. Hypertension and dyslipidemia are one of the major risk factor for stroke while homocysteine is a less well-documented risk factor. The purpose of this study was to know the correlation between homocysteine and dyslipidemia in ischaemic stroke patients with and without hypertension. This study is a cross sectional study; the sample were taken consecutively. All sample matched with inclusion and exclusion criteria, demography data and blood sample were taken. Demography data was analyzed using descriptive statistic, to analyze the relation, we used Chi-Square test. p value value = 0,009. A significant correlation between homocysteine and dyslipidemia might be because both of them have an important role in the acceleration of the atherosclerotic formation by activation platelet and thrombus, but we still need further study to get more explanation about the relation.

  6. Folate Deficiency Is Associated With Oxidative Stress, Increased Blood Pressure, and Insulin Resistance in Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kožich, V.; Krijt, J.; Sokolová, J.; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Šilhavý, Jan; Oliyarnyk, O.; Kazdová, L.; Kurtz, T. W.

    2013-01-01

    Roč. 26, č. 1 (2013), s. 135-140 ISSN 0895-7061 R&D Projects: GA MZd(CZ) NS10036; GA MŠk(CZ) ME10019; GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : blood pressure * ectopic fat accumulation * folate deficiency * homocysteine * hypertension * oxidative stress * spontaneously hypertensive rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

  7. In-treatment stroke volume predicts cardiovascular risk in hypertension

    DEFF Research Database (Denmark)

    Lønnebakken, Mai T; Gerdts, Eva; Boman, Kurt

    2011-01-01

    substudy. Results: During follow-up, a total of 91 primary endpoints occurred. At baseline, lower left ventricular stroke volume was associated with smaller body size, female sex, lower left ventricular mass and stress-corrected midwall shortening, higher relative wall thickness and total peripheral...... with higher risk of cardiovascular events {hazard ratio 1.69 per 1 SD (6 ml/m2.04) lower stroke volume [95% confidence interval (CI) 1.35–2.11], P mass and concentric geometry and in a secondary model also independent of stress-corrected midwall shortening...... resistance, more concentric left ventricular geometry and impaired diastolic relaxation (all P indexed for height2.04 was associated...

  8. Arterial hypertension and stroke: cardiac and neurological aspects of secondary prevention

    Directory of Open Access Journals (Sweden)

    L.A. Geraskina

    2014-01-01

    Full Text Available This article considers the pathogenetic mechanisms of stroke in arterial hypertension (AH with special emphasis on comorbid neurological and cardiac disorders. It presents the cardiac and neurological aspects of the current strategy of medical therapy within the secondary prevention of poststroke cardiovascular events. The secondary prevention of cardiovascular events in patients who have sustained ischemic stroke in the presence of AH involves the use of not only antihypertensive drugs, but also adequate antiplatelet therapy and statins. The most important part is assigned to the prevention and treatment of cognitive impairments, which also promotes increased patient treatment adherence and improved poststroke prognosis, including longer survival and better quality of life.

  9. No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Alves Christiano RR

    2012-04-01

    Full Text Available Abstract Background Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR. Findings Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 ± 1.5 vs. Pl: 12.2 ± 1.7 nmol·mg-1; p = 0.87, heart (Cr: 11.5 ± 1.8 vs. Pl: 14.6 ± 1.1 nmol·mg-1; p = 0.15, plasma (Cr: 67.7 ± 9.1 vs. Pl: 56.0 ± 3.2 nmol·mg-1; p = 0.19, plantaris (Cr: 10.0 ± 0.8 vs. Pl: 9.0 ± 0.8 nmol·mg-1; p = 0.40, and EDL muscle (Cr: 14.9 ± 1.4 vs. Pl: 17.2 ± 1.5 nmol·mg-1; p = 0.30. Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p > 0.05. Conclusions Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.

  10. Effects of losartan combined with exercise training in spontaneously hypertensive rats

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    L.F. Azevedo

    2003-11-01

    Full Text Available We investigate whether combined treatment with losartan, an angiotensin II receptor blocker, and exercise training (ET in spontaneously hypertensive rats (SHR would have an additive effect in reducing hypertension and improving baroreflex sensitivity when compared with losartan alone. Male SHR (8 weeks old were assigned to 3 groups: sedentary placebo (SP, N = 16, sedentary under losartan treatment (SL, N = 11; 10 mg kg-1 day-1, by gavage, and ET under losartan treatment (TL, N = 10. ET was performed on a treadmill 5 days/week for 60 min at 50% of peak VO2, for 18 weeks. Blood pressure (BP was measured with a catheter inserted into the carotid artery, and cardiac output with a microprobe placed around the ascending aorta. The baroreflex control of heart rate was assessed by administering increasing doses of phenylephrine and sodium nitroprusside (iv. Losartan significantly reduced mean BP (178 ± 16 vs 132 ± 12 mmHg and left ventricular hypertrophy (2.9 ± 0.4 vs 2.5 ± 0.2 mg/g, and significantly increased baroreflex bradycardia and tachycardia sensitivity (1.0 ± 0.3 vs 1.7 ± 0.5 and 2.0 ± 0.7 vs 3.2 ± 1.7 bpm/mmHg, respectively in SL compared with SP. However, losartan combined with ET had no additional effect on BP, baroreflex sensitivity or left ventricular hypertrophy when compared with losartan alone. In conclusion, losartan attenuates hypertension and improves baroreflex sensitivity in SHR. However, ET has no synergistic effect on BP in established hypertension when combined with losartan, at least at the dosage used in this investigation.

  11. EXERCISE TRAINING IMPROVES CARDIOVASCULAR AUTONOMIC ACTIVITY AND ATTENUATES RENAL DAMAGE IN SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Octávio Barbosa Neto

    2013-03-01

    Full Text Available Experiments were performed to determine the influence of exercise training by swimming on cardiovascular autonomic control and renal morphology in spontaneously hypertensive rats (SHR and Wystar-Kyoto (WKY rats. Sedentary normotensive (SN, trained normotensive (TN, sedentary hypertensive (SH, and trained hypertensive (TH rats were included in this study. Arterial pressure (AP, heart rate (HR, means of power spectral analysis of HR (HRV and systolic AP variability (SAPV were recorded in baseline conditions. Following, the HR baroreflex and autonomic tonus control were assessed. At the end, all animals were euthanized and their kidneys were excised to evaluate renal damage. Resting bradycardia was observed in TH and TN rats compared with their respective sedentary animals (p < 0.05. Exercise training attenuated AP in TH vs. SH (p < 0.001. The LF component of HRV and SAPV were lower in TH than SH (p < 0.05. The LF/HF relation was lower in TH than SH and SN (p < 0.05. TN and TH rats showed a sympathetic tonus reduction in comparison to SN and SH rats (p < 0.001. The TH presented an increased vagal tonus compared to SH (p < 0.05. Exercise training improved baroreflex control of HR in TH group versus SH (p < 0.05. The TH showed a lower number of sclerotic glomeruli compared to SH (p < 0.005. The exercise training decrease the glomerular indexes in TN and TH (p < 0.05. Further analysis showed a significant correlation between sympathetic nervous activity and AP levels (p < 0.05. A positive association was also found between sympathetic nervous activity and glomerular index (p < 0.05. Therefore, the exercise training reduces AP and attenuates renal damage. In addition, the attenuation of renal injury was associated with lower sympathetic activity. These findings strongly suggest that exercise training may be a therapeutic tool for improving structure and renal function in hypertensive individuals.

  12. Dietary Approaches to Stop Hypertension Diet and Incidence of Stroke: Results From 2 Prospective Cohorts.

    Science.gov (United States)

    Larsson, Susanna C; Wallin, Alice; Wolk, Alicja

    2016-04-01

    High adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower risk of hypertension, the major risk factor for stroke. We examined whether adherence to the DASH diet is inversely associated with the incidence of stroke. The study population comprised 74 404 men and women (45-83 years of age), without stroke at baseline, from the Cohort of Swedish Men and the Swedish Mammography Cohort. Diet was assessed with a food-frequency questionnaire. A modified DASH diet score was created based on consumption of vegetables, fruits, legumes and nuts, whole grains, low-fat dairy, red meat and processed meat, and sweetened beverages. Stroke cases were identified through linkage to the Swedish National Patient and Cause of Death Registers. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards regression model. During 882 727 person-years (mean, 11.9 years) of follow-up, 3896 ischemic strokes, 560 intracerebral hemorrhages, and 176 subarachnoid hemorrhages were ascertained. The modified DASH diet score was statistically significantly inversely associated with the risk of ischemic stroke (P for trend=0.002), with a multivariable relative risk of 0.86 (95% confidence interval, 0.78-0.94) for the highest versus the lowest quartile of the score. The modified DASH diet score was nonsignificantly inversely associated with intracerebral hemorrhage (corresponding relative risk=0.81; 95% confidence interval, 0.63-1.05) but was not associated with subarachnoid hemorrhage. These findings indicate that high adherence to the DASH diet is associated with a reduced risk of ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01127698 and NCT01127711 for the Swedish Mammography Cohort and the Cohort of Swedish Men, respectively. © 2016 American Heart Association, Inc.

  13. Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

    OpenAIRE

    Valenti, Vitor E.; Abreu, Luiz Carlos de; Fonseca, Fernando L. A.; Adami, Fernando; Sato, Monica A.; Vanderlei, Luiz Carlos M.; Ferreira, Lucas Lima; Rodrigues, Luciano M.; Ferreira, Celso

    2013-01-01

    OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4...

  14. Effect of different frequencies of music on blood pressure regulation in spontaneously hypertensive rats.

    Science.gov (United States)

    Akiyama, Kayo; Sutoo, Den'etsu

    2011-01-03

    The effect of different frequencies of music on brain function was investigated through measurement of blood pressure in spontaneously hypertensive rats (SHR). Previous studies indicated that exposure to Mozart's music (K. 205) leads to increased calcium/calmodulin-dependent dopamine synthesis in the brain, and that the subsequent increase in dopamine reduces blood pressure via D(2) receptors. The present study demonstrated that the blood pressure-reducing response was dependent on the frequency, and was markedly greater at 4 k-16 kHz compared with lower frequencies. These findings suggest that music containing high-frequency sounds stimulates dopamine synthesis, and might thereby regulate and/or affect various brain functions. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Camila P. Jordão

    Full Text Available OBJECTIVE: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats (SHR and Wistar Kyoto rats (WKY were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively. The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal’s body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%. Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving

  16. Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats

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    Yanru Sun

    2018-02-01

    Full Text Available Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL, which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs. We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

  17. Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats.

    Science.gov (United States)

    Sun, Yanru; Han, Mingfeng; Shen, Zhenhuang; Huang, Haibo; Miao, Xiaoqing

    2018-02-01

    Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

  18. Alterations in substance P binding in brain nuclei of spontaneously hypertensive rats

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    Shigematsu, K.; Niwa, M.; Kurihara, M.; Castren, E.; Saavedra, J.M.

    1987-01-01

    Substance P binding sites were characterized in brain nuclei of young (4-wk-old) and adult (16-wk-old) spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Young SHR presented higher affinity constants (K/sub A/) than young WKY. The changes were restricted to locus coeruleus, the area postrema, the dorsal motor nucleus of the vagus, and to discrete areas located in lobes 9 and 10 of the vermis cerebelli of SHR. There were no differences in the maximal binding capacity (B/sub max/) except in the nucleus ambiguus where the B/sub max/ was lower than WKY. Conversely, the number of substance P binding sites was higher in the locus coeruleus, the nucleus tegmentalis dorsalis, the nucleus ambiguus, the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the inferior olivary nucleus, and lobes 9 and 10 of the vermis cerebelli of adult SHR when compared with adult WKY. The results support the hypothesis of a role for brain substance P in blood pressure regulation and in genetic hypertension in rats

  19. Alveolar bone healing process in spontaneously hypertensive rats (SHR). A radiographic densitometry study.

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    Manrique, Natalia; Pereira, Cassiano Costa Silva; Garcia, Lourdes Maria Gonzáles; Micaroni, Samuel; Carvalho, Antonio Augusto Ferreira de; Perri, Sílvia Helena Venturoli; Okamoto, Roberta; Sumida, Doris Hissako; Antoniali, Cristina

    2012-01-01

    Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats.

  20. Long-Term Effect of an Aqueous Fraxinus excelsior L. Seed Extract in Spontaneously Hypertensive Rats

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    Noemi López-Carreras

    2014-01-01

    Full Text Available The effect of long-term intake of different doses (20, 40, and 60 mg/kg/day of a Fraxinus excelsior L. seed extract (FESE on spontaneously hypertensive rats (SHR was evaluated. Water was used as control and captopril (50 mg/kg/day was used as positive control. Systolic blood pressure, body weight, and food and liquid intake were registered weekly in SHR. The antioxidant and vascular relaxing properties of FESE were also studied in these animals. The development of hypertension was attenuated in the groups treated with captopril or FESE. The antihypertensive effect was more accentuated in the captopril group than in the FESE groups, and it was paradoxically more accentuated in the groups treated with 20 mg/kg/day or 40 mg/kg/day of FESE than in the group treated with the highest dose of this extract. Body weight gain and food intake increased in the FESE groups. After removing the corresponding antihypertensive treatment, the arterial blood pressure and the body weight of the FESE treated animals returned to control values. In addition, FESE increased plasma antioxidant capacity and decreased plasma and liver malondialdehyde levels. Moreover, acetylcholine relaxation improved in the aorta rings from the FESE treated rats.

  1. Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats

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    Hano, T.; Jeng, Y.; Rho, J.

    1989-01-01

    We compared the overflow of endogenous norepinephrine during electrical field stimulation, the norepinephrine content, and the rate of initial neuronal uptake of [3H]norepinephrine in synaptosomes isolated from hypothalamus and brainstem of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 7 and 13 weeks of age. The synaptosomes of two rats, a SHR and a WKY rat control, were simultaneously processed and subjected to the same electrical field stimulation. The overflow of endogenous norepinephrine during electrical stimulation (2 Hz, 2 minutes) in the hypothalamic synaptosomes of 7-week-old SHR was significantly greater, whereas the overflow of 13-week-old SHR was equivalent to the age-matched WKY rat. The norepinephrine content of synaptosomes was about the same in SHR and age-matched controls. There was also significantly enhanced [3H]norepinephrine uptake in the hypothalamic synaptosomes of young SHR, but neither the hypothalamic nor the brainstem samples of 13-week-old SHR showed any significant difference in their rate of [3H]norepinephrine uptake. These data are similar to those we observed (unpublished observations) in perfused mesenteric artery system in which norepinephrine release was significantly elevated during periarterial nerve stimulation only in young SHR. Thus, these results suggest that a parallel enhancement of norepinephrine release in hypothalamus with that of peripheral nervous system may play an important role during development of hypertension in young SHR

  2. Vascular oxidative stress precedes high blood pressure in spontaneously hypertensive rats.

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    Nabha, Linda; Garbern, Jessica C; Buller, Carolyn L; Charpie, John R

    2005-01-01

    This study examines whether longitudinal antioxidant treatment initiated in prehypertensive spontaneously hypertensive rats (SHR) can attenuate vascular oxidant stress and prevent blood pressure elevation during development. Male SHR and age-matched Wistar-Kyoto rats (WKY) were treated from 6 to 11 weeks of age with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl) (1 mmol/l in drinking water), a membrane-permeable superoxide dismutase mimetic. Mean systolic blood pressures (SBPs) were measured by tail-cuff Agonist-induced and basal O2- production was measured in thoracic aortas of 6- and 11-week-old SHR and WKY by lucigenin-derived chemiluminescence and oxidative fluorescent microscopy, respectively. SBP of 6-week-old SHR (131 +/- 5 mmHg) and WKY (130 +/- 4 mmHg) were not different; however, 11-week-old SHR SBP (171 +/- 4 mmHg) was significantly greater (p = .0001) than 11-week-old WKY SBP (143 +/- 5 mmHg). Tempol treatment completely, but reversibly, prevented this age-related rise in SHR SBP (SHR + Tempol: 137 +/- 4 mmHg; p oxidative stress prevents the age-related development of high blood pressure in an animal model of genetic hypertension.

  3. Enalapril alters the formation of the collagen matrix in spontaneously hypertensive rats

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    Alfredo de Souza Bomfim

    2003-07-01

    Full Text Available OBJECTIVE: To assess the effect of the inhibition of the angiotensin-converting enzyme on the collagen matrix (CM of the heart of newborn spontaneously hypertensive rats (SHR during embryonic development. METHODS: The study comprised the 2 following groups of SHR (n=5 each: treated group - rats conceived from SHR females treated with enalapril maleate (15 mg. kg-1.day-1 during gestation; and nontreated group - offspring of nontreated females. The newborns were euthanized within the first 24 hours after birth and their hearts were removed and processed for histological study. Three fields per animal were considered for computer-assisted digital analysis and determination of the volume densities (Vv of the nuclei and CM. The images were segmented with the aid of Image Pro Plus® 4.5.029 software (Media Cybernetics. RESULTS: No difference was observed between the treated and nontreated groups in regard to body mass, cardiac mass, and the relation between cardiac and body mass. A significant reduction in the Vv[matrix] and a concomitant increase in the Vv[nuclei] were observed in the treated group as compared with those in the nontreated group. CONCLUSION: The treatment with enalapril of hypertensive rats during pregnancy alters the collagen content and structure of the myocardium of newborns.

  4. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

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    Omotayo O. Erejuwa

    2012-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP in spontaneously hypertensive rats (SHR. It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2 and glutathione S-transferase (GST were significantly downregulated while total antioxidant status (TAS and activities of GST and catalase (CAT were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

  5. Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

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    Luana U. Pagan

    2015-04-01

    Full Text Available Background: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF development and cardiac remodeling in aging spontaneously hypertensive rats (SHR. Methods: Sixteen month old SHR (n=50 and normotensive Wistar-Kyoto (WKY, n=35 rats were divided into sedentary (SED and exercised (EX groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. Statistical analyses: ANOVA and Tukey or Mann-Whitney, and Goodman test. Results: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Conclusion: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

  6. Long-term low intensity physical exercise attenuates heart failure development in aging spontaneously hypertensive rats.

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    Pagan, Luana U; Damatto, Ricardo L; Cezar, Marcelo D M; Lima, Aline R R; Bonomo, Camila; Campos, Dijon H S; Gomes, Mariana J; Martinez, Paula F; Oliveira, Silvio A; Gimenes, Rodrigo; Rosa, Camila M; Guizoni, Daniele M; Moukbel, Yasmin C; Cicogna, Antonio C; Okoshi, Marina P; Okoshi, Katashi

    2015-01-01

    Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF) development and cardiac remodeling in aging spontaneously hypertensive rats (SHR). Sixteen month old SHR (n=50) and normotensive Wistar-Kyoto (WKY, n=35) rats were divided into sedentary (SED) and exercised (EX) groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. ANOVA and Tukey or Mann-Whitney, and Goodman test. Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV) systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

  7. Effect of tempol on myocardial vascular remodeling in female spontaneously hypertensive rats.

    Science.gov (United States)

    Bonacasa, B; Hernández, I; Fenoy, F J; Quesada, T; López, B

    2012-08-01

    The present study evaluated whether the treatment with the superoxide anion dismutase mimetic tempol prevents the worsening in hypertension and in myocardial vascular remodeling induced by ovariectomy in female spontaneously hypertensive rats (SHR). Experiments were performed in ten week old female SHRs randomly assigned to the groups: intact (INT: given vehicle; INT+T: treated with tempol, 90 mg/kg/day), ovariectomized (OVX: vehicle and OVX+T: tempol, respectively) and ovariectomized treated with 17β-estradiol (OVX+E2 and OVX+E2+T). Evolution of systolic blood pressure (SBP) was determined every other week in lightly restrained awake rats using a noninvasive computerized tail-cuff plethysmography system. At 18 weeks of age the heart was excised and structural changes in histopathological sections of coronary vessels were quantified on a computerized imaging system analyzer. SBP was significantly lower in female SHRs treated with tempol compared to the values measured in untreated animals. In the vascular remodeling of myocardial arterioles, OVX+T rats had a lower media cross sectional area and media-to-lumen ratio than those observed in the OVX SHR. Interestingly, treatment with tempol in the presence of estradiol (in female INT and OVX+E2 SHR ) increased media cross sectional area and wall-to-lumen ratio of myocardial arterioles, despite the fact that it lowered arterial pressure in those groups. These results indicate that tempol prevents arterial hypertension and blunts myocardial vascular remodeling in ovariectomized SHR. Paradoxically, when tempol is given in presence of estradiol it has a detrimental effect on myocardial arteriolar remodeling.

  8. Influence of long-term arotinolol treatment on myocardial mechanics and ventricular myosin isoenzymes in spontaneously hypertensive rats.

    Science.gov (United States)

    Takeda, N; Ohkubo, T; Iwai, T; Tanamura, A; Nagano, M

    1990-01-01

    Alterations in myocardial mechanics and left ventricular myosin isoenzymes by long-term treatment of hypertension with arotinolol were examined in spontaneously hypertensive rats. Approximately 20 mg/kg/day arotinolol was administered to 22-week-old male spontaneously hypertensive rats for 8-10 weeks. There was no significant difference in systolic blood pressure between arotinolol-treated and untreated rats. However, ventricular weight tended to decrease in the arotinolol-treated group, although not significantly. There were no significant differences in isometric developed tension and dT/dtmax of isolated left ventricular papillary muscles between the arotinolol-treated and untreated groups. The left ventricular myosin isoenzyme pattern, on the other hand, obtained by pyrophosphate gel electrophoresis, showed a significant shift toward VM-1 as a result of long-term arotinolol treatment.

  9. Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Klippel, Brunella F; Duemke, Licia B; Leal, Marcos A; Friques, Andreia G F; Dantas, Eduardo M; Dalvi, Rodolfo F; Gava, Agata L; Pereira, Thiago M C; Andrade, Tadeu U; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

    2016-01-01

    It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1-adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively

  10. Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension

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    Lipsitz Lewis A

    2004-10-01

    Full Text Available Abstract Background This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP. The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals. Methods We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years. BP and blood flow velocities (BFV from middle cerebral arteries (MCA were measured during the Valsalva maneuver (VM using transcranial Doppler ultrasound. Results A new technique, multimodal pressure-flow analysis (MMPF, was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR and BFV (BFVR signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts. Conclusion In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.

  11. Clinical review: Therapy for refractory intracranial hypertension in ischaemic stroke.

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    Jüttler, Eric; Schellinger, Peter D; Aschoff, Alfred; Zweckberger, Klaus; Unterberg, Andreas; Hacke, Werner

    2007-01-01

    The treatment of patients with large hemispheric ischaemic stroke accompanied by massive space-occupying oedema represents one of the major unsolved problems in neurocritical care medicine. Despite maximum intensive care, the prognosis of these patients is poor, with case fatality rates as high as 80%. Therefore, the term 'malignant brain infarction' was coined. Because conservative treatment strategies to limit brain tissue shift almost consistently fail, these massive infarctions often are regarded as an untreatable disease. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view, suggesting that mortality rates may be reduced to approximately 20%. However, critics have always argued that the reduction in mortality may be outweighed by an accompanying increase in severe disability. Due to the lack of conclusive evidence of efficacy from randomised trials, controversy over the benefit of these treatment strategies remained, leading to large regional differences in the application of this procedure. Meanwhile, data from randomised trials confirm the results of former observational studies, demonstrating that hemicraniectomy not only significantly reduces mortality but also significantly improves clinical outcome without increasing the number of completely dependent patients. Hypothermia is another promising treatment option but still needs evidence of efficacy from randomised controlled trials before it may be recommended for clinical routine use. This review gives the reader an integrated view of the current status of treatment options in massive hemispheric brain infarction, based on the available data of clinical trials, including the most recent data from randomised trials published in 2007.

  12. Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

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    Tufik Sergio

    2007-03-01

    Full Text Available Abstract Background Paradoxical sleep deprivation (PSD associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group. To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg or testosterone (0.5 mg/kg or 1.0 mg/kg administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role

  13. Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project.

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    Lip, G Y; Blann, A D; Farooqi, I S; Zarifis, J; Sagar, G; Beevers, D G

    2001-06-01

    While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged ictus 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.

  14. Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

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    Chen Su-Hong

    2015-01-01

    Full Text Available Radix Paeoniae Alba (Baishao, RPA has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD- induced hypertensive rats and spontaneously hypertensive rats (SHR was constantly received either RPA extract (25 or 75 mg/kg or captopril (15 mg/kg all along the experiments. As a result, RPA extract (75 mg/kg could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT and aspartate transaminase (AST in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO and endothelin (ET levels.

  15. Acute Treatment with Lauric Acid Reduces Blood Pressure and Oxidative Stress in Spontaneously Hypertensive Rats.

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    Alves, Naiane Ferraz Bandeira; de Queiroz, Thyago Moreira; de Almeida Travassos, Rafael; Magnani, Marciane; de Andrade Braga, Valdir

    2017-04-01

    The effects of acute administration of lauric acid (LA), the most abundant medium-chain fatty acid of coconut oil, on blood pressure, heart rate and oxidative stress were investigated in spontaneously hypertensive rats (SHR). Intravenous doses of LA reduced blood pressure in a dose-dependent fashion (1, 3, 4, 8 and 10 mg/kg) in both SHR and Wistar Kyoto rats. LA (10 -8 to 3 × 10 -3 M) induced vasorelaxation in isolated superior mesenteric artery rings of SHR in the presence (n = 7) or absence (n = 8) of functional endothelium [maximum effect (ME) = 104 ± 3 versus 103 ± 4%]. After exposure to KCl (60 mM), LA also induced concentration-dependent vasorelaxation (n = 7) compared to that under Phe-induced contraction (ME = 113.5 + 5.1 versus 104.5 + 4.0%). Furthermore, LA-induced vasorelaxation in vessels contracted with S(-)-BayK8644 (200 nM), a L-type Ca 2+ channel agonist (ME = 91.4 + 4.3 versus 104.5 + 4.0%, n = 7). Lastly, LA (10 -3 M) reduced NADPH-dependent superoxide accumulation in the heart (18 ± 1 versus 25 ± 1 MLU/min/μg protein, n = 4, p < 0.05) and kidney (82 ± 3 versus 99 ± 4 MLU/min/μg protein, n = 4, p < 0.05). Our data show that LA reduces blood pressure in normotensive and hypertensive rats. In SHR, this effect might involve Ca +2 channels in the resistance vessels and by its capability of reducing oxidative stress in heart and kidneys. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. Fish protein improves the total antioxidant status of streptozotocin-induced diabetes in spontaneously hypertensive rat.

    Science.gov (United States)

    Boukortt, Farida Ouda; Girard, Aurélie; Prost, Josiane L; Ait-Yahia, Dalila; Bouchenak, Malika; Belleville, Jacques

    2004-11-01

    We measured the effects of fish protein (FP) on blood pressure, glycemia and antioxidant status in spontaneously hypertensive (SH) rats with streptozotocin-induced diabetes (STZ). Two groups of 12 rats each were fed 20% casein (C) or FP for 2 months. The total antioxidant status of blood and organs (liver, kidney and heart) was measured by the KRL test. Antioxidant enzyme activities (G-Px, G-Red, and SOD) and antioxidant substances (GSH, NO) were determined in organs, and vitamin C in plasma. FP lowered blood pressure in SH rats, but not in SH-STZ. Blood and plasma antioxidant status increased 35% and 9%, respectively, with FP in SH-STZ compared to SH rats; when compared to C, these values were more enhanced. SOD activity values were elevated with FP in SH-STZ rats, compared to the C diet, regardless of organ. Higher kidney NO and heart GSH values were noted in SH-STZ rats than SH. In SH rats fed FP, the GSH value was 2.26 times higher in liver, and NO was 3 times higher in heart. Higher NO was noted in kidney (1.84 times) and heart (1.91 times), GSH in heart (1.79 times), and vitamin C in plasma (+46%) in SH-STZ rats with FP than with C. Fish protein has a beneficial effect on blood pressure in SH rats but not in SH-STZ, and plays an important role in antioxidative defense. This protein may be useful in future treatments of such diseases as diabetes and hypertension.

  17. CT findings and prognosis of spontaneous (hypertensive) intracerebralhematoma associated with intraventricular perforation

    International Nuclear Information System (INIS)

    Sogabe, Koichiro; Gyoten, Tetsuya; Masuda, Tsutomu; Hondo, Hideki; Matsumoto, Keizo

    1982-01-01

    The prognosis of spontaneous hypertensive intracerebral hematoma associated with the intraventricular hemorrhage were discussed with the base of computerized tomography (CT) findings in their acute stage. 104 (47%) out of 219 patients with hypertensive intracerebral hemorrhage revealed intraventricular hemorrhage in our service from January 1978 to December 1980. In these cases infratentorial, cerebellar and pontine hemorrhage were not included. Namely, 22 out of 93 cases of putaminal hemorrhage, 47 out of 61 cases in thalamic type, 30 out of 39 cases in combined type and 5 out of 26 cases in subcortical type were demonstrated the ventricular hemorrhage by CT examination, respectively. In early period of CT utilization, the ventricular hemorrhage had generally been accepted as one of serious signs from the knowledges, which had been obtained from postmortem examination in such cases. Recent experiences, however, suggested that cases of intracerebral hematoma with the ventricle rupture were not always resulted to the poor prognosis. Cases, which had extension of the hematoma to the 3rd and 4th ventricle, were clearly divided into two contradictory group, namely, poor and good prognostic group. They showed nearly equal occurance. However, it was noted that cases with the cast formation below the third ventricle resulted poor prognosis. Statistical analysis of our cases led the following conclusions i.e. the influencing factors of the poor outcome are: hematoma size is larger than 3x3 cm, combination of acute ventricular enlargement, disappearance of the ambient cistern and hypothalamic extension of hematoma; cast formation of blood in the 3rd and 4th ventricle. (J.P.N.)

  18. Long-term antihypertensive effect of a soluble cocoa fiber product in spontaneously hypertensive rats

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    Sandra Fernández-Vallinas

    2016-05-01

    Full Text Available Background and Methods: This study evaluates the antihypertensive effect of long-term intake of a soluble cocoa fiber product (SCFP. Different doses of SCFP were evaluated (200, 400, and 800 mg/kg/day and a dose of 800 mg/kg/day of beta-glucan 0.75 (BETA-G was used as a standard fiber. Water, a neutral vehicle, was used as negative control, and 50 mg/kg/day captopril was used as positive control. Systolic blood pressure (SBP was measured weekly by the tail cuff method. Body weight, food, and liquid intake were also registered weekly in the rats from 10 to 24 weeks of life. Glucose, total cholesterol, and triglyceride levels; redox status; and the angiotensin-converting enzyme activity were also studied in the plasma samples of these animals. Results: Throughout the 10 weeks of treatment, captopril and SCFP (400 mg/kg/day demonstrated blood pressure lowering effects in the spontaneously hypertensive rats (p0.05; n=8. When the corresponding antihypertensive treatment, was disrupted the SBP values of the 400 mg/kg/day SCFP treated animals returned to control values (p>0.05; n=8. In addition, the SCFP significantly decreased (p<0.05; n=4 the glucose, cholesterol, and triglyceride levels and also the liver and plasma malondaldehyde levels. Moreover, the SCFP slightly increased the reduced glutathione levels in the liver. Conclusion: The SCFP could be used to control the blood pressure of hypertensive subjects for a long period of time and could improve metabolic complications associated to cardiovascular diseases.

  19. Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

    Science.gov (United States)

    Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2012-01-01

    Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. PMID:22427863

  20. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

    Directory of Open Access Journals (Sweden)

    Ana Isabel Garcia Diaz

    2016-04-01

    Full Text Available The Wistar Kyoto (WKY rat and the spontaneously hypertensive (SHR rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN and metabolic syndrome, respectively. Novel transgenic (Tg strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP under the rat elongation factor 1 alpha (EF1a promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades.

  1. Age-related changes in body fluid volumes in young spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Von Dreele, M.M.

    1988-01-01

    The authors have measured total body water (TBW, by dessiccation), extracellular fluid volume (ECF, Na 2 35 SO 4 space), and plasma volume (PV, radioiodinated serum albumin space) in 5-sec-butyl-5-ethyl-2-thiobarbituric acid and sodium salt (Inactin)-anesthetized spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats aged 12-60 days. Interstitial fluid volume (ISF) was calculated as ECF minus PV. Changes in TBW, ECF, and ISF were largely a function of age in both strains, which is typical of developing mammals. Further analysis revealed that although these volumes were significantly larger in SHR before 25 days of age, after 30 days no difference existed between the strains. Before 25 days of age, when SHR's TBW was expanded, no weight difference was seen between the strains. However, once TBW was normalized (after 30 days), WKY was significantly heavier than SHR. The ISF volume was preferentially enlarged in SHR, although PV was also periodically greater. ISF normalized at the time when blood pressure becomes significantly higher in SHR, when plasma aldosterone falls to WKY values in SHR and when renal function is approaching adult levels. Thus the return of ECF (ISF) to normal values may be a result of decreased aldosterone-dependent volume retention or to diuresis induced by increasing blood pressure in an animal whose renal function is close to maturity

  2. Amlodipine reduces the antimigratory effect of diclofenac in spontaneously hypertensive rats.

    Science.gov (United States)

    Rodrigues, Stephen Fernandes; Dossantos, Rosangela Aparecida; de Oliveira, Maria Aparecida; Rastelli, Viviani Milan; Nucci, Gilberto de; Tostes, Rita de Cássia; Nigro, Dorothy; Carvalho, Maria Helena; Fortes, Zuleica B

    2008-05-01

    Amlodipine, an antihypertensive drug, and diclofenac, an antiinflammatory drug, may generally be combined, particularly in elderly patients; therefore, the potential for their interaction is high. We aim to determine if amlodipine interferes with the antimigratory effect of diclofenac. For this, male spontaneously hypertensive rats (SHRs) were treated with either diclofenac (1 mg.kg.d, 15 d) alone or combined with amlodipine (10 mg.kg.d, 15 d). Leukocyte rolling, adherence, and migration were studied by intravital microscopy. Diclofenac did not change (180.0 +/- 2.3), whereas amlodipine combined (163.4 +/- 5.1) or not (156.3 +/- 4.3) with diclofenac reduced the blood pressure (BP) levels in SHR (183.1 +/- 4.4). Diclofenac and amlodipine reduced leukocyte adherence, migration, and ICAM-1 expression, whereas only diclofenac reduced rolling leukocytes as well. Combined with amlodipine, the effect of the diclofenac was reduced. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, P-selectin, PECAM-1, L-selectin, or CD-18 expressions. No difference could be found in plasma concentrations of both drugs given alone or in association. In conclusion, amlodipine reduces leukocyte migration in SHR, reducing endothelial cell ICAM-1 expression. Amlodipine reduces the effect of the diclofenac, possibly by the same mechanism. A pharmacokinetic interaction as well as an effect on the other adhesion molecules tested could be discarded.

  3. Efficacy and Safety of Gwakhyangjeonggi-San Retention Enema in Normal Rats and Spontaneously Hypertensive Rats

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    Eunyoung Song

    2013-01-01

    Full Text Available The purpose of this study is to establish a protocol of retention-enema experiments and evaluate the antihypertensive effect and the safety of Gwakhyangjeonggi-san retention enema. Normal and spontaneously hypertensive rats (SHRs were divided into treatment and control groups, respectively. We applied the Gwakhyangjeonggi-san extract by decoction and 0.9% NaCl in each group, estimated the blood pressure and body weight, and performed HPLC analysis. ALT, AST, BUN, and creatinine were examined. The systolic blood pressure within each group in normal rats differed significantly in time effect, and so did the diastolic blood pressure in the treatment group of normal rats. The systolic, diastolic, and mean blood pressure showed significant differences in group effect in the treatment group of the SHRs. The time effect of the body weight in both groups of normal rats differed significantly, so did group × time and time effects in both groups of SHRs. AST, ALT, BUN, and creatinine showed no significant difference between groups. We concluded that the Gwakhyangjeonggi-san retention enema has a hypotensive effect in normal rats within the regular range of blood pressure, but an antihypertensive effect in SHRs. Also, the intervention is safe and does not affect the liver and kidney functions in normal rats.

  4. Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H

    1989-01-01

    Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8-14.7 mm Hg......) and stop-flow pressures (40.0-42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY...... anaesthetized control group of SPRD, the feedback response was lower, and the feedback curve was displaced to the right with the Tp at 15.9 nl/min, significantly higher than in the control group (p less than 0.001). Although the steady state level also was reached within 2 min, the clearly biphasic pattern...

  5. Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats.

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    Vincent Chin-Hung Chen

    Full Text Available Attention deficit hyperactivity disorder (ADHD is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR animal model was adopted. Significantly decreased serum C-reactive protein (CRP was detected in rats of Wistar Kyoto (WKY high-taurine group and significantly decreased interleukin (IL-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC and mean amplitude of low-frequency fluctuation (mALFF in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

  6. Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats

    Science.gov (United States)

    Chen, Vincent Chin-Hung; Hsu, Tsai-Ching; Chen, Li-Jeng; Chou, Hong-Chun

    2017-01-01

    Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats. PMID:28700674

  7. Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-01-01

    The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

  8. Vasoconstrictor responses to 5-hydroxytryptamine in the autoperfused hindquarters of spontaneously hypertensive rats.

    Science.gov (United States)

    Calama, E; Morán, A; Ortiz de Urbina, A V; Martín, M L; San Román, L

    2004-06-01

    In this work we studied the responses and receptors involved in the effects of intra-arterial 5-hydroxytryptamine (5-HT) in the in situ autoperfused hindquarters of spontaneously hypertensive rats (SHR). Intra-arterial administration of the highest doses (50-1,000 ng/kg) produced a vasoconstrictor effect that was inhibited by ritanserin (a selective 5-HT2 receptor antagonist), SB 206553 (a selective 5-HT(2B/2C) receptor antagonist) and spiperone (a nonspecific 5-HT(1/2A) receptor antagonist), and was mimicked by alpha-methyl-5-HT (a selective 5-HT2 receptor agonist) and m-CPP (a selective 5-HT2C receptor agonist), but not by the intra-arterial administration of BW 723C86, a selective 5HT2B receptor agonist. SB 206553 and spiperone inhibited alpha-methyl-5HT-induced vasoconstriction in the hindquarters of SHR. Our data suggest that the vasoconstrictor response induced by 5-HT in the autoperfused hindquarters of SHR is mainly mediated by the activation of 5-HT2A and 5-HT2C receptors. Copyright 2004 S. Karger AG, Basel

  9. Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat.

    Science.gov (United States)

    El Bardai, S; Lyoussi, B; Wibo, M; Morel, N

    2001-05-01

    The hypotensive effects of the water extract of Marrubium vulgare L. and Foeniculum vulgare L. were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Oral administration of Marrubium or Foeniculum extract lowered the systolic blood pressure of SHR but not of WKY. In SHR, Foeniculum but not Marrubium treatment increased water, sodium and potassium excretion. Ex vivo as well as in vitro, Marrubium extract inhibited the contractile responses of rat aorta to noradrenaline and to KCl (100 mM). Inhibition was greater in aorta from SHR compared to WKY and was not affected by the NO synthase inhibitor N-nitro-L-arginine. Vascular effects of Foeniculum extract were less pronounced than those of Marrubium and were blocked by N-nitro-L-arginine. These results indicate that hypotensive activity of Marrubium and Foeniculum extracts seems to be mediated through different pathways: Foeniculum appeared to act mainly as a diuretic and a natriuretic while Marrubium displayed vascular relaxant activity.

  10. Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats.

    Science.gov (United States)

    Chen, Vincent Chin-Hung; Hsu, Tsai-Ching; Chen, Li-Jeng; Chou, Hong-Chun; Weng, Jun-Cheng; Tzang, Bor-Show

    2017-01-01

    Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

  11. Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats.

    Science.gov (United States)

    Baracho, Nilo César do Vale; Arruda, Guilherme D'Andréa Saba; Alves, Lidinei José; Carneiro, Márcio Felipe Salomon; Siqueira, Matheus Teodoro Grilo; Arango, Héctor Gustavo; Marcos dos Reis, José

    2008-01-01

    High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR). Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. The use of generic drug and similars (A and B) drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.

  12. A CLA enriched diet improves organ damage associated with the metabolic syndrome in spontaneous hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Rodriguez, I.; Pulido-Camarillo, E.; Hernandez-Diaz, E.; Alexander-Aguilera, A.; Garcia, H.S.

    2011-07-01

    The purpose of this study was to provide evidence that dietary CLA can prevent the pathogenesis of metabolic syndrome in tissue structure, suggesting potential benefits in the onset of this syndrome. Wistar male spontaneous hypertensive rats (SHR), were classified into two groups that were fed a standard diet for eight weeks: one with 7.5% sunflower oil (V-SHR group), and the other with 6% sunflower oil and 1.5% CLA (CLA-SHR group). A control healthy group consisted of Kyoto-Wistar male rats fed the standard diet with 7.5% sunflower oil. The animals were sacrificed, and sections of liver, kidneys and aorta were fixed in 10% formaldehyde, and then stained with Hematoxylin and Eosin. Only in the V-SHR group, the stain of the aorta indicated irregular endothelial morphology; liver parenchyma was characterized by an infiltration of inflammatory neutrophils, fibrosis, thickening of the portal vein epithelium, hepatocyte hyperplasia and steatosis. The renal tissue of this group evidenced hyperplasia in the cells of the endothelial of Bowman's capsule. Abnormal histological changes were not observed in either the control group of the rats fed with CLA, suggesting a protective role of CLA in the onset of metabolic syndrome.

  13. Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Shumei Mao

    2015-01-01

    Full Text Available Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE and its possible mechanisms in spontaneously hypertensive rats (SHR rats. Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats were used in this study. Rats were, respectively, given EFE (EFE group, captopril (captopril group, or phosphate-buffered saline (PBS (normal control group and SHR group for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP and diastolic blood pressure (DBP were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II, aldosterone (Ald, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α in plasma were determined by radioimmunoassay, and serum nitric oxide (NO concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL. After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity.

  14. Increased sensitivity to cocaine-induced analgesia in Spontaneously Hypertensive Rats (SHR

    Directory of Open Access Journals (Sweden)

    Takahashi Reinaldo N

    2007-02-01

    Full Text Available Abstract This study examined the analgesic effect of cocaine in Spontaneously Hypertensive Rats (SHR, which are considered a suitable model for the study of attention deficit hyperactivity disorder (ADHD, and in Wistar (WIS rats of both sexes using the hot-plate test. In addition, we tested whether habituation to the unheated hot-plate apparatus, that "normalizes" the basal hypoalgesic phenotype of SHR, alters the subsequent cocaine-induced analgesia (CIA in this strain. SHR of both sexes were hypoalgesic compared to WIS rats in the hot-plate test and showed higher sensitivity to CIA. Habituation to the unheated hot-plate reduced the basal nociceptive latency of SHR, suggesting cognitive/emotional modulation of pain in this strain, but did not alter the magnitude of CIA. The present study shows increased sensitivity to CIA in SHR, which may be related to abnormalities in the mesocorticolimbic dopaminergic system. Further studies using SHR strain may reveal new information on the neurobiological mechanisms underlying ADHD and its co-morbidity with drug addiction.

  15. Qiliqiangxin Enhances Cardiac Glucose Metabolism and Improves Diastolic Function in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Jingfeng Wang

    2017-01-01

    Full Text Available Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The present study aims to explore whether Qiliqiangxin (QL can benefit cardiac diastolic function in spontaneously hypertensive rat (SHR through enhancement of cardiac glucose metabolism. Fifteen 12-month-old male SHRs were randomly divided into QL-treated, olmesartan-treated, and saline-treated groups. Age-matched WKY rats served as normal controls. Echocardiography and histological analysis were performed. Myocardial glucose uptake was determined by 18F-FDG using small-animal PET imaging. Expressions of several crucial proteins and key enzymes related to glucose metabolism were also evaluated. As a result, QL improved cardiac diastolic function in SHRs, as evidenced by increased E′/A′and decreased E/E′ (P<0.01. Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and apoptosis (P<0.01. An even higher myocardial glucose uptake was illustrated in QL-treated SHR group (P<0.01. Moreover, an increased CS activity and ATP production was observed in QL-treated SHRs (P<0.05. QL enhanced cardiac glucose utilization and oxidative phosphorylation in SHRs by upregulating AMPK/PGC-1α axis, promoting GLUT-4 expression, and regulating key enzymes related to glucose aerobic oxidation such as HK2, PDK4, and CS (P<0.01. Our data suggests that QL improves cardiac diastolic function in SHRs, which may be associated with enhancement of myocardial glucose metabolism.

  16. Autoradiography of dopamine receptors and dopamine uptake sites in the spontaneously hypertensive rat

    International Nuclear Information System (INIS)

    Kujirai, K.; Przedborski, S.; Kostic, V.; Jackson-Lewis, V.; Fahn, S.; Cadet, J.L.

    1990-01-01

    We examined the status of dopamine (DA) D1 and D2 receptors by using [3H]SCH 23390 and [3H]spiperone binding, respectively, and DA uptake sites by using [3H]mazindol binding in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. SHR showed significantly higher [3H]SCH 23390 and [3H]spiperone binding in the caudate-putamen (CPu), the nucleus accumbens (NAc) and the olfactory tubercle (OT) in comparison to the SD rats. There were no significant differences in [3H]mazindol-labeled DA uptake sites between the two strains. Unilateral 6-hydroxydopamine (6-OHDA) injection into the striatum resulted in more than 90% depletion of DA uptake sites in the CPu in both strains. 6-OHDA-induced DA depletion was associated with significant increases in striatal [3H]spiperone binding which were of similar magnitude in the SD rats (+64.1%) and SHR (+51.3%). There were only small decreases (-5.4%) in D1 receptor binding in the dorsolateral aspect of the CPu in the SHR, whereas there were no changes in striatal D1 receptors in the SD rats. These results indicate that, although the SHR have higher concentrations of both D1 and D2 receptors in the basal ganglia, these receptors are regulated in a fashion similar to DA receptors in SD rats after 6-OHDA-induced striatal DA depletion

  17. Autoradiography of dopamine receptors and dopamine uptake sites in the spontaneously hypertensive rat

    Energy Technology Data Exchange (ETDEWEB)

    Kujirai, K.; Przedborski, S.; Kostic, V.; Jackson-Lewis, V.; Fahn, S.; Cadet, J.L. (Columbia Univ., New York, NY (USA))

    1990-11-01

    We examined the status of dopamine (DA) D1 and D2 receptors by using (3H)SCH 23390 and (3H)spiperone binding, respectively, and DA uptake sites by using (3H)mazindol binding in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. SHR showed significantly higher (3H)SCH 23390 and (3H)spiperone binding in the caudate-putamen (CPu), the nucleus accumbens (NAc) and the olfactory tubercle (OT) in comparison to the SD rats. There were no significant differences in (3H)mazindol-labeled DA uptake sites between the two strains. Unilateral 6-hydroxydopamine (6-OHDA) injection into the striatum resulted in more than 90% depletion of DA uptake sites in the CPu in both strains. 6-OHDA-induced DA depletion was associated with significant increases in striatal (3H)spiperone binding which were of similar magnitude in the SD rats (+64.1%) and SHR (+51.3%). There were only small decreases (-5.4%) in D1 receptor binding in the dorsolateral aspect of the CPu in the SHR, whereas there were no changes in striatal D1 receptors in the SD rats. These results indicate that, although the SHR have higher concentrations of both D1 and D2 receptors in the basal ganglia, these receptors are regulated in a fashion similar to DA receptors in SD rats after 6-OHDA-induced striatal DA depletion.

  18. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Durand, M.T.; Mota, A.L.; Barale, A.R.; Castania, J.A.; Fazan, R. Jr.; Salgado, H.C.

    2012-01-01

    The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR

  19. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Durand, M.T.; Mota, A.L. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Barale, A.R. [Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG (Brazil); Castania, J.A.; Fazan, R. Jr.; Salgado, H.C. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-16

    The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.

  20. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    M.T. Durand

    2012-05-01

    Full Text Available The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric was measured in conscious male spontaneously hypertensive (SHR and normotensive control rats (NCR; Wistar; 18-22 weeks subjected to electrical stimulation of the aortic depressor nerve (ADN under thiopental anesthesia. The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15 and NCR (N = 14; hypotension = NCR (4194 ± 336 to 3695 ± 463 ms vs SHR (3475 ± 354 to 4494 ± 300 ms; bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms vs SHR (1911 ± 323 to 1852 ± 431 ms, and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms vs SHR (4849 ± 918 to 4926 ± 646 ms; mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms vs SHR (5638 ± 648 to 6777 ± 624 ms. In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent in conscious SHR compared to NCR.

  1. A Novel Hemp Seed Meal Protein Hydrolysate Reduces Oxidative Stress Factors in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Abraham T. Girgih

    2014-12-01

    Full Text Available This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH in spontaneously hypertensive rats (SHR. Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old SHRs were divided into three groups (8 rats/group and fed diets that contained 0.0%, 0.5% or 1.0% (w/w HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC and superoxide dismutase (SOD, catalase (CAT and total peroxides (TPx levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05 increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.

  2. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 3 (2015), s. 295-301 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.643, year: 2015

  3. Fat-specific transgenic expression of resistin in the spontaneously hypertensive rat impairs fatty acid re-esterification

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kazdová, L.; Cahová, M.; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Wang, J.; Qi, N.; Kurtz, T. W.

    2006-01-01

    Roč. 30, č. 7 (2006), s. 1157-1159 ISSN 0307-0565 R&D Projects: GA ČR(CZ) GA301/03/0751; GA MZd(CZ) NB7403; GA MŠk(CZ) 1M0520 Grant - others:HHMI(US) 55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneously hypertensive rat * transgenic resistin * fatty acid reesterification Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.055, year: 2006

  4. Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Morrissey, C.; Grieve, I.; Heinig, M.; Atanur, S.; Petretto, E.; Pravenec, Michal; Hubner, N.; Aitman, T. J.

    2011-01-01

    Roč. 43, č. 21 (2011), s. 1207-1218 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GA301/08/0166; GA MŠk(CZ) ME10019 Institutional research plan: CEZ:AV0Z50110509 Keywords : eQTL * spontaneously hypertensive rat * quantitative trait transcript * sequence variation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.735, year: 2011

  5. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Czech Academy of Sciences Publication Activity Database

    Malínská, H.; Oliyarnyk, O.; Škop, V.; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, L.; Pravenec, Michal

    2016-01-01

    Roč. 11, č. 3 (2016), e0150924 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * spontaneously hypertensive rat * transgenic * C-reactive protein * dicarbonyl stress * metformin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.806, year: 2016

  6. Effect of Chronic Social Stress on Endothelial Function of the Mesenteric Artery of Normotensive and Spontaneously Hypertensive Rats

    OpenAIRE

    Kaprinay B.; Bernatova I.; Sotnikova R.

    2016-01-01

    The aim of the work was to study the effect of chronic social stress induced by increased population density, “crowding stress” on blood pressure and endothelial function of arteries of male normotensive Wistar and spontaneously hypertensive (SHR) rats. Based on the results, we assume that social stress-induced reduction in endothelium-dependent relaxation and increased blood pressure of SHR rats is most likely associated with decreased bioavailability of nitric oxide.

  7. Effects of transgenic expression of dopamine beta hydroxylase (Dbh) gene on blood pressure in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šilhavý, Jan; Mir, S.A.; Vaingankar, S. M.; Wang, J.; Kurtz, T. W.

    2016-01-01

    Roč. 65, č. 6 (2016), s. 1039-1044 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP301/12/0696; GA TA ČR(CZ) TA02010013 Institutional support: RVO:67985823 Keywords : spontaneously hypertensive rat * transgenic * dopamine beta hydroxylase * catecholamines * blood pressure * left ventricular mass Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.461, year: 2016

  8. Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Trnovská, J.; Škop, V.; Marková, I.; Malínská, H.; Hüttl, M.; Kazdová, L.; Bardová, Kristina; Tauchmannová, Kateřina; Vrbacký, Marek; Nůsková, Hana; Mráček, Tomáš; Kopecký, Jan; Houštěk, Josef

    2017-01-01

    Roč. 66, č. 6 (2017), s. 917-924 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * spontaneously hypertensive rat * quantitative trait loci * transgenic * Wars2 gene * mitochondrial proteosynthesis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 1.461, year: 2016

  9. Role of FAT/CD36 in novel PKC isoform activation in heart of spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Klevstig, M. J.; Marková, I.; Burianová, J.; Kazdová, L.; Pravenec, Michal; Nováková, O.; Novák, F.

    2011-01-01

    Roč. 357, 1-2 (2011), s. 163-169 ISSN 0300-8177 R&D Projects: GA ČR(CZ) GD305/08/H037; GA MŠk(CZ) ME08006 Grant - others:Univerzita Karlova(CZ) SVV33779266 Institutional research plan: CEZ:AV0Z50110509 Keywords : CD36 * novel PKC * spontaneously hypertensive rat * insulin resistance Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.057, year: 2011

  10. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  11. Effects of high dose olive leaf extract on haemodynamic and oxidative stress parameters in normotensive and spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Dekanski Dragana

    2014-01-01

    Full Text Available Antihypertensive activity of natural antioxidant, olive leaf extract (OLE is known, but its influence on cardiovascular system when administered in a high dose has not been investigated yet. Our aim was to determine the acute effects of excessive intake of standardized OLE on blood pressure, heart rate and oxidative status in both spontaneously hypertensive rats and normotensive Wistar rats. Systolic arterial pressure and heart rate were measured using a tail-cuff, pneumatic pulse detector, before, 60 and 120 minutes after intragastric OLE administration. Activities of catalase, glutathione peroxidase, superoxide dismutase (SOD and glutathione reductase in erythrocytes, as well as lipid peroxidation in plasma (pTBARS were measured at the same time points, spectrophotometrically. High-dose OLE did not influence blood pressure, heart rate and pTBARS in normotensive rats, while SOD, catalase, and glutathione reductase activities significantly increased. The same dose significantly decreased blood pressure in hypertensive rats, but increased pTBARS and SOD activity. Excessive oral intake of OLE induced moderate hypotensive effects in spontaneously hypertensive rats only, suggesting absence of harmful haemodynamic effects after oral overdose in both rats strain. However, its prooxidative role when given in high dose in hypertensive organism should not be neglected. [Projekat Ministarstva nauke Republike Srbije, br. 175096

  12. Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

    Energy Technology Data Exchange (ETDEWEB)

    Sharkey, Leslie C., E-mail: shark009@umn.edu [Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, St. Paul, MN 55108 (United States); Radin, M. Judith, E-mail: radin.1@osu.edu [Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210 (United States); Heller, Lois, E-mail: lheller@d.umn.edu [Department of Biomedical Sciences, University of Minnesota Medical School—Duluth, 1035 University Drive, Duluth, MN 55812-3031 (United States); Rogers, Lynette K., E-mail: Lynette.Rogers@nationwidechildrens.org [Center for Perinatal Research, The Research Institute at Nationwide Children' s Hospital, 700 Childrens Drive, Columbus, OH 43205 (United States); Tobias, Anthony [Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, St. Paul, MN 55108 (United States); Matise, Ilze, E-mail: imatise.vh@gmail.com [Veterinary Population Medicine Department, University of Minnesota, 1365 Gortner Ave, St Paul, MN (United States); Wang, Qi, E-mail: wangx890@umn.edu [Clinical and Translational Science Institute (CTSI), University of Minnesota, 717 Delaware St SE, Minneapolis, MN (United States); Apple, Fred S., E-mail: apple004@umn.edu [Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and University of Minnesota, 701 Park Ave S, Minneapolis, MN USA (United States); McCune, Sylvia A., E-mail: sylvia.mccune@skybeam.com [Department of Integrative Physiology, University of Colorado at Boulder, 354 UCB, Clare Small 114, Boulder, CO 80309 (United States)

    2013-11-15

    Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids

  13. Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

    International Nuclear Information System (INIS)

    Sharkey, Leslie C.; Radin, M. Judith; Heller, Lois; Rogers, Lynette K.; Tobias, Anthony; Matise, Ilze; Wang, Qi; Apple, Fred S.; McCune, Sylvia A.

    2013-01-01

    Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids

  14. Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

    Science.gov (United States)

    Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

    2015-12-30

    The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the

  15. [Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats].

    Science.gov (United States)

    Hernández, Noelina; De Sanctis, Juan B; Losada, Mercedes; Torres, Sonia H; Sosa, Amparo; Rivas, Miriam

    2011-09-01

    Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/- 0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/- 3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF-alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/- 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs. 30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05; EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs. 7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.

  16. Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Bedussi, Beatrice; Naessens, Daphne M. P.; de Vos, Judith; Olde Engberink, Rik; Wilhelmus, Micha M. M.; Richard, Edo; ten Hove, Malyssa; VanBavel, Ed; Bakker, Erik N. T. P.

    2017-01-01

    Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer's disease. In animal models of hypertension, many of Alzheimer's disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid beta accumulation and blood brain

  17. Long-Term Stroke Risk Due to Partial White-Coat or Masked Hypertension Based on Home and Ambulatory Blood Pressure Measurements: The Ohasama Study.

    Science.gov (United States)

    Satoh, Michihiro; Asayama, Kei; Kikuya, Masahiro; Inoue, Ryusuke; Metoki, Hirohito; Hosaka, Miki; Tsubota-Utsugi, Megumi; Obara, Taku; Ishiguro, Aya; Murakami, Keiko; Matsuda, Ayako; Yasui, Daisaku; Murakami, Takahisa; Mano, Nariyasu; Imai, Yutaka; Ohkubo, Takayoshi

    2016-01-01

    The prognostic significance of white-coat hypertension (WCHT) is controversial, and different findings on self-measured home measurements and 24-h ambulatory monitoring make identifying WCHT difficult. We examined whether individuals with partially or completely defined WCHT, as well as masked hypertension, as determined by different out-of-office blood pressure measurements, have a distinct long-term stroke risk. We followed 1464 participants (31.8% men; mean age, 60.6±10.8 years) in the general population of Ohasama, Japan, for a median of 17.1 years. A first stroke occurred in 212 subjects. Using sustained normal blood pressure (events/n=61/776) as a reference, adjusted hazard ratios for stroke (95% confidence intervals; events/n) were 1.38 (0.82-2.32; 19/137) for complete WCHT (isolated office hypertension), 2.16 (1.36-3.43; 29/117) for partial WCHT (either home or ambulatory normotension with office hypertension), 2.05 (1.24-3.41; 23/100) for complete masked hypertension (both home and ambulatory hypertension with office normotension), 2.08 (1.37-3.16; 38/180) for partial masked hypertension (either home or ambulatory hypertension with office normotension), and 2.46 (1.61-3.77; 42/154) for sustained hypertension. When partial WCHT and partial masked hypertension groups were further divided into participants only with home hypertension and those only with ambulatory hypertension, all subgroups had a significantly higher stroke risk (adjusted hazard ratio ≥1.84, P≤0.04). In conclusion, impacts of partial WCHT as well as partial masked hypertension for long-term stroke risk were comparable to those of complete masked hypertension or sustained hypertension. We need both home and 24-h ambulatory blood pressure measurements to evaluate stroke risk accurately. © 2015 American Heart Association, Inc.

  18. Aldosterone binding in isolated tubules. IV. Autoradiography along the nephron of the spontaneously hypertensive rat

    International Nuclear Information System (INIS)

    Farman, N.; Bonvalet, J.P.

    1985-01-01

    The binding of aldosterone was studied in tubular segments isolated by microdissection from kidneys of spontaneously hypertensive (SHR, n = 8), Kyoto normotensive (KWR, n = 8), and normal Wistar (NWR, n = 6) rats with an autoradiographic technique on dry film. All animals had been previously adrenalectomized. Kidney pyramids were incubated in vitro before microdissection with collagenase and 2 X 10(-9) M [ 3 H]aldosterone in the presence or absence of an excess of unlabeled aldosterone. In addition, the displacement of the binding by 10 times excess dexamethasone or aldosterone was examined in the cortical and medullary collecting tubule of SHR and KWR to assess the specificity of binding sites. In the three groups, no specific nuclear labeling was detectable in the proximal tubule. The highest specific nuclear labeling was found in the distal portions of the nephron, and intermediate values were present along the loop of Henle. In the cortical collecting tubule, the most specific mineralocorticoid segment, the specific nuclear binding, expressed in silver grains per unit surface, was significantly elevated in SHR (16.1 +/- 1.5) and KWR (13.7 +/- 1.5) as compared with NWR (10.2 +/- 0.8, P less than 0.001 and less than 0.05, respectively). The difference between SHR and KWR did not reach statistical significance. In the medullary collecting tubule, binding was higher in SHR (14.3 +/- 1.6) than in both KWR (8.7 +/- 1.0, P less than 0.005) and NWR (10.1 +/- 0.9, P less than 0.025)

  19. Nonselective Blocking of the Sympathetic Nervous System Decreases Detrusor Overactivity in Spontaneously Hypertensive Rats

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    Chang-Shin Park

    2012-04-01

    Full Text Available The involuntary dual control systems of the autonomic nervous system (ANS in the bladder of awake spontaneously hypertensive rats (SHRs were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO objectively as a core symptom of an overactive bladder. SHRs (n = 6 showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%. DO frequency decreased from 0.98 ± 0.22 min−1 to 0.28 ± 0.19 min−1 (p < 0.01, and DO pressure decreased from 3.82 ± 0.57 cm H2O to 1.90 ± 0.86 cm H2O (p < 0.05. This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.

  20. Ultrafine carbon black attenuates the antihypertensive effect of captopril in spontaneously hypertensive rats.

    Science.gov (United States)

    Zhang, Xinru; Chen, Yiyong; Wei, Hongying; Qin, Yu; Hao, Yu; Zhu, Yidan; Deng, Furong; Guo, Xinbiao

    2014-12-01

    Particulate matter (PM) has been associated with increased blood pressure (BP) by affecting renin-angiotensin system (RAS) on a systemic level in spontaneously hypertensive rats (SHR). RAS in SHR is also an important target for the angiotensin converting enzyme (ACE) inhibitors such as captopril. We aimed to determine if ultrafine carbon black (UCB) could affect antihypertensive effect of captopril in SHR. The rats were randomly divided into six groups. Group 1 did not receive intratracheal instillation; group 2 received saline instillation plus captopril administration; groups 3, 4 and 5 received 0.15 mg/kg, 0.45 mg/kg and 1.35 mg/kg UCB per instillation plus captopril administration, respectively; group 6 received 1.35 mg/kg UCB instillation only. Rats in the above groups were intratracheally instilled with saline or UCB once every two days for three times and captopril was administered to group 2-5 after the final UCB treatment, once a day for one week. The BP was measured 24 h after each intratracheal instillation. During captopril administration and 24 h after last captopril administration, we measured BP every two days for four times. Our results showed that UCB at the dose of 1.35 mg/kg induced pulmonary and systemic inflammation in SHR. Captopril reduced BP in rats exposed to 0, 0.15 and 0.45 mg/kg UCB seven and eleven days after the first UCB instillation, and had no effect on BP in rats exposed to 1.35 mg/kg UCB. Captopril also reduced angiotensin II (AngII) in rats exposed to saline. The reduction, however, was attenuated with increasing doses of UCB. We conclude that UCB attenuated the antihypertensive effect of captopril in SHR, and the effect was accompanied by a systemic increase in the concentration of AngII.

  1. Calcemic response to parathyroid hormone in spontaneously hypertensive rats: role of calcitriol.

    Science.gov (United States)

    Hsu, C H; Patel, S; Young, E W

    1987-12-01

    Spontaneously hypertensive rats (SHR) display lower ionized calcium (Pca++) concentrations when compared with normotensive Wistar Kyoto rats (WKY). This could be attributable to renal wasting of calcium, decreased intestinal calcium absorption, or decreased bone resorption, processes that are integrated by the parathyroid hormone (PTH) and vitamin D systems. We have studied the calcemic response to PTH infusion (3 U/hr/100 gm) for 5 hours in 13-week-old SHR and WKY. Pre-PTH Pca++ concentration of nonfasted SHR (4.68 +/- 0.06 mg/dl, N = 8) was significantly lower than that of WKY (4.84 +/- 0.03, N = 8, P less than 0.05). Pca++ concentration rose in both nonfasted WKY and SHR at the end of PTH infusion, but the increment of Pca++ in SHR (0.29 +/- 0.05 mg/dl, N = 8) was lower than that in WKY (Pca++, 0.60 +/- 0.07 mg/dl, N = 8, P less than 0.01). Urinary calcium excretion (UcaV) and creatinine clearances (Ccr) before and after PTH infusion were not different between WKY and SHR. Despite an increased filtered load of calcium, UcaV was not greater in either WKY or SHR during the PTH infusion. Pretreatment of SHR with calcitriol 50 ng intravenous bolus injection, which had no effect on Pca++ concentration (0.02 +/- 0.03 mg/dl, N = 7), corrected the lower calcemic response to PTH in SHR, and the Pca++ increment was no longer different between WKY (0.57 +/- 0.07 mg/dl, N = 7) and SHR (0.62 +/- 0.09, N = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Ouabain binding to cultured vascular smooth muscle cells of the spontaneously hypertensive rat

    International Nuclear Information System (INIS)

    Hopp, L.; Khalil, F.; Tamura, H.; Kino, M.; Searle, B.M.; Tokushige, A.; Aviv, A.

    1986-01-01

    The binding of ouabain and K + to the Na + pump were analyzed in serially passed cultured vascular smooth muscle cells (VSMCs) originating from spontaneously hypertensive (SH) Wistar-Kyoto (WKY), and American Wistar (W) rats. The techniques have utilized analyses of displacement of [ 3 H]ouabain by both unlabeled ouabain and K + from specific binding sites on the VSMCs. The authors have found that 1) each of the VSMC preparations from the three rat strains appeared to demonstrate one population of specific ouabain receptors (Na + pumps); 2) the number of Na + pump units of both the SH and WKY rats was significantly lower than the number of Na + pump units of W rat VSMCs; 3) the equilibrium dissociation constant values (μM) for ouabain in VSMCs of SH and WKY rats were similar but were significantly higher than that of VSMCs derived from W rats; and 4) among the VSMCs originating from the three rat strains, the apparent equilibrium dissociation constant value for K + (mM) was the lowest in those of the SH rat compared with VSMCs of the WKY rat and W rat. Previous studies have demonstrated increased passive Na + and K + transport rate constants of SH rat VSMCs compared with either W or WKY rat cells. These findings suggest the possibility of higher permeabilities of the SH cells. They propose that the combined effect of a low number of Na + pump units with higher permeabilities to Na + and K + predisposes VSMCs of the SH rat to disturbances in their cellular ionic regulation. These genetic defects, if they occur in vivo, may lead to an increase in the vascular tone

  3. Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

    Directory of Open Access Journals (Sweden)

    M.V. Borgo

    2011-08-01

    Full Text Available Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR. Female SHR were divided into four groups (N = 7 each: sham-operated (SHAM, sham-operated and treated with tamoxifen (10 mg/kg by gavage for 90 days (TAMOX, ovariectomized (OVX, and ovariectomized and treated with tamoxifen (OVX+TAMOX. Mean arterial pressure (MAP, heart rate (HR, coronary perfusion pressure (CPP, and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively in the OVX+TAMOX group compared to the OVX group (P < 0.01. The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg when compared to the OVX group (P < 0.01 and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05. Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01. Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

  4. Mechanisms of improved aortic stiffness by arotinolol in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Wugang Zhou

    Full Text Available OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR. METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO was measured in human aortic endothelial cells (HAECs by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹, arotinolol (30 mg·kg-1·d⁻¹ for 8 weeks. Central arterial pressure (CAP and pulse wave velocity (PWV were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS and eNOS phosphorylation (p-eNOS of HAECs or aortas were analyzed by western blotting. RESULTS: Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker. Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. CONCLUSIONS: Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries.

  5. Mechanisms of improved aortic stiffness by arotinolol in spontaneously hypertensive rats.

    Science.gov (United States)

    Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

    2014-01-01

    This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹), arotinolol (30 mg·kg-1·d⁻¹) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries.

  6. Effects of centrally acting antihypertensive drugs on the microcirculation of spontaneously hypertensive rats

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    Estato V.

    2004-01-01

    Full Text Available We investigated the acute effects of centrally acting antihypertensive drugs on the microcirculation of pentobarbital-anesthetized spontaneously hypertensive rats (SHR. The effects of the sympatho-inhibitory agents clonidine and rilmenidine, known to activate both alpha2-adrenoceptors and nonadrenergic I1-imidazoline binding sites (I1BS in the central nervous system, were compared to those of dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H -pyrrol-2-yl-amine hydrochloride (LNP 509, which selectively binds to the I1BS. Terminal mesenteric arterioles were observed by intravital microscopy. Activation of the central sympathetic system with L-glutamate (125 µg, ic induced marked vasoconstriction of the mesenteric microcirculation (27 ± 3%; N = 6, P < 0.05. In contrast, the marked hypotensive and bradycardic effects elicited by intracisternal injection of clonidine (1 µg, rilmenidine (7 µg and LNP 509 (60 µg were accompanied by significant increases in arteriolar diameter (12 ± 1, 25 ± 10 and 21 ± 4%, respectively; N = 6, P < 0.05. The vasodilating effects of rilmenidine and LNP 509 were two-fold higher than those of clonidine, although they induced an identical hypotensive effect. Central sympathetic inhibition elicited by baclofen (1 µg, ic, a GABA B receptor agonist, also resulted in vasodilation of the SHR microvessels. The acute administration of clonidine, rilmenidine and LNP 509 also induced a significant decrease of cardiac output, whereas a decrease in systemic vascular resistance was observed only after rilmenidine and LNP 509. We conclude that the normalization of blood pressure in SHR induced by centrally acting antihypertensive agents is paralleled by important vasodilation of the mesenteric microcirculation. This effect is more pronounced with substances acting preferentially (rilmenidine or exclusively (LNP 509 upon I1BS than with those presenting important alpha2-adrenergic activity (clonidine.

  7. Physician assessment of stroke risk in hypertensive patients in the Middle East and Africa: results of the action survey.

    Science.gov (United States)

    Badr, Kamal F; Boudia, Khereddine M Merad; Alami, Mohamed; Khoja, Waleed A; Belhani, Ali B; Nawar, Moustafa; Ragy, Hany; Ishaq, Mohammad; Baron, J M Muscat; Hammoudeh, Ayman J; De Mar Youssef, Suzan S; Nakhle, Reine M; Chalfoun, Amale G

    2007-01-01

    In the absence of reliable, contemporary national data, the ACTION survey was designed to: a) provide preliminary data on stroke risk in the MEA (Middle East and Africa); b) describe the contribution of specific cardiovascular risk factors; 3) assess blood pressure (BP) control. This was a multi-center observational study in nine countries in the MEA region. From 2003 to 2005, 562 physicians from a variety of specialties recorded observations of cardiovascular risk factors in 4,747 hypertensive patients, aged 54-80 years. The 10-year absolute stroke risk was calculated using a scoring system based on the Framingham Heart Study observations, and comparisons made with an age-matched cohort. The mean 10-year stroke risk was estimated at 22.7% and was significantly higher for men (25.4%) than for women (19.5%) (P age-matched Framingham cohort, the estimated stroke risk in our population was almost double, and was significantly higher for females (212%) than for males (192%) (P < .001). Hypertension, diabetes, left ventricular hypertrophy, and smoking were major contributing risk factors, as were physical inactivity and elevated cholesterol. Blood pressure was controlled in only 18% of the population and in 12% of diabetics. Physicians of all specialties were willing to participate in stroke risk assessment. The risk of stroke in hypertensive patients in the MEA region is high, and is higher than would be predicted using Framingham data, particularly for females. Hypertension appears to be poorly controlled in more than 80% of hypertensive patients in the MEA region.

  8. Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling.

    Directory of Open Access Journals (Sweden)

    Wei-Min Luo

    Full Text Available Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1 signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRsand elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional

  9. Hypertension

    Science.gov (United States)

    ... Hypertension Triglycerides Featured Resource Find an Endocrinologist Search Hypertension September 2017 Download PDFs English Espanol Editors Fady ... Additional Resources MedlinePlus (NIH) Mayo Clinic What is hypertension? Hypertension, or high blood pressure, is a leading ...

  10. Age-related changes in immunoreactivity for dopamine β-hydroxylase in carotid body glomus cells in spontaneously hypertensive rats.

    Science.gov (United States)

    Kato, Kouki; Fushuku, Seigo; Yamamoto, Yoshio

    2017-07-01

    The purpose of this study was to investigate immunoreactivity for dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in carotid body (CB) glomus cells in spontaneously hypertensive rats (SHR/Izm) at 4 (prehypertensive stage), 8 (early stage of developmental hypertension), 12 (later stage of developmental hypertension), and 16weeks of age (established hypertensive stage). Age-matched Wistar Kyoto rats (WKY/Izm) were used as controls. Staining properties for TH were similar between both strains at each age. Regarding DBH immunostaining, although some glomus cells showed intense DBH immunoreactivity at 4weeks of age, these cells were rarely observed at 8, 12, and 16weeks of age in WKY/Izm. In SHR/Izm, intense DBH immunoreactivity was observed in some glomus cells at 4weeks of age, these cells were also observed at 8 and 12weeks of age, and their number increased at 16weeks of age. An image analysis showed that the percentage of DBH-immunopositive glomus cells in WKY/Izm was approximately 30% at 4weeks of age and significantly decreased to approximately 10% at 8, 12, and 16weeks of age (pcells was similar in both strains at 4weeks of age, but became significantly lower in WKY/Izm and higher in SHR/Izm with increase in age (pcells plays an important role in the regulation of neurotransmission between CB and afferent nerves during developmental hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Effect of exercise training on Ca{sup 2+} release units of left ventricular myocytes of spontaneously hypertensive rats

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    Carneiro-Júnior, M.A. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Amadeu, M.A.; Oliveira, E.M. [Universidade de São Paulo, Laboratório de Bioquímica e Biologia Molecular do Exercício, Escola de Educação Física e Esportes, São Paulo, SP (Brazil); Felix, L.B. [Universidade Federal de Viçosa, Departamento de Engenharia Elétrica, Viçosa, MG (Brazil); Cruz, J.S. [Universidade Federal de Minas Gerais, Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Belo Horizonte, MG (Brazil); Mill, J.G. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Natali, A.J.; Prímola-Gomes, T.N. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil)

    2014-08-29

    In cardiomyocytes, calcium (Ca{sup 2+}) release units comprise clusters of intracellular Ca{sup 2+} release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca{sup 2+} sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca{sup 2+} sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F{sub 0}), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca{sup 2+} sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F{sub 0}, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of

  12. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests.

    Science.gov (United States)

    López-Gil, Xavier; Amat-Roldan, Iván; Tudela, Raúl; Castañé, Anna; Prats-Galino, Alberto; Planas, Anna M; Farr, Tracy D; Soria, Guadalupe

    2014-01-01

    The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

  13. Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

    Directory of Open Access Journals (Sweden)

    Womersley Jacqueline S

    2011-12-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1 in SHR striatum. Consistent with this observation, the dopamine clearance time (T100 was increased in SHR. These results suggest that the chronic mild stress of

  14. AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats

    Science.gov (United States)

    Yang, Qin; Xue, Hong-Mei; Wong, Wing-Tak; Tian, Xiao-Yu; Huang, Yu; Tsui, Stephen KW; Ng, Patrick KS; Wohlfart, Paulus; Li, Huige; Xia, Ning; Tobias, Silke; Underwood, Malcolm John; He, Guo-Wei

    2011-01-01

    BACKGROUND AND PURPOSE Nitric oxide (NO) plays an important role in endothelial function, and impaired NO production is involved in hypertension. Therefore, compounds that regulate endothelial NO synthase (eNOS) may be of therapeutic benefit. A novel, low molecular weight compound AVE3085 is a recently developed compound with the ability to enhance eNOS transcription. The present study investigated the effects of AVE3085 in endothelial dysfunction associated with hypertension. EXPERIMENTAL APPROACH Spontaneously hypertensive rats (SHRs) were treated with AVE 3085 (10 mg·kg·day−1, orally) for 4 weeks. Isometric force measurement was performed on rings of isolated aortae in organ baths. Protein expression of eNOS, phosphorylated-eNOS and nitrotyrosine in the aortae were examined by Western blotting. mRNA for eNOS in rat aortae were examined by reverse-transcriptase polymerase chain reaction (RT-PCR). KEY RESULTS AVE3085 greatly improved endothelium-dependent relaxations in the aortae of SHRs. This functional change was accompanied by up-regulated expression of eNOS protein and mRNA, enhanced eNOS phosphorylation and decreased formation of nitrotyrosine. Furthermore, AVE3085 treatment reduced the blood pressure in SHR without affecting that of hypertensive eNOS−/− mice. CONCLUSIONS AND IMPLICATIONS The eNOS-transcription enhancer AVE3085 restored impaired endothelial function in a hypertensive model. The present study provides a solid basis for the potential development of eNOS-targeting drugs to restore down-regulated eNOS, as a new strategy in hypertension. PMID:21385179

  15. Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats.

    Science.gov (United States)

    Hussein, Ghazi; Goto, Hirozo; Oda, Shinobu; Sankawa, Ushio; Matsumoto, Kinzo; Watanabe, Hiroshi

    2006-04-01

    We investigated the effects of a dietary astaxanthin (ASX-O) on oxidative parameters in spontaneously hypertensive rats (SHR), by determination of the level of nitric oxide (NO) end products nitrite/nitrate (NO2-/NO3-) and lipid peroxidation in ASX-O-treated SHR. Oral administration of the ASX-O significantly reduced the plasma level of NO2-/NO3- compared to the control vehicle (pASX-O- and olive oil-treated groups. We also analyzed the post-treatment effects of ASX-O on the vascular tissues by examining the changes in the aorta and coronary arteries and arterioles. The dietary ASX-O showed significant reduction in the elastin bands in the rat aorta (pASX-O can modulate the oxidative condition and may improve vascular elastin and arterial wall thickness in hypertension.

  16. Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension.

    Science.gov (United States)

    Iliescu, Radu; Tudorancea, Ionut; Irwin, Eric D; Lohmeier, Thomas E

    2013-10-01

    The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

  17. Identification of defective CD36 as a quantitative trait locus for cardiovascular risk factor clustering in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Landa, Vladimír; Zídek, Václav; Křen, Vladimír

    2001-01-01

    Roč. 2, č. 2 (2001), s. 161-169 ISSN 1389-2029 R&D Projects: GA ČR(CZ) GA301/00/1636; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015; GA ČR(CZ) GA305/00/1646 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 (fatty acid transporter) * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology

  18. Comparative study of the antihypertensive activity of Marrubium vulgare and of the dihydropyridine calcium antagonist amlodipine in spontaneously hypertensive rat.

    Science.gov (United States)

    El Bardai, Sanae; Lyoussi, Badiaa; Wibo, Maurice; Morel, Nicole

    2004-08-01

    Water extract of Marrubium vulgare is widely used as antihypertensive treatment in folk medicine. We have compared the effect of 10-week-long treatment with amlodipine or Marrubium water extract on systolic blood pressure (SBP), cardiovascular remodeling and vascular relaxation in spontaneously hypertensive rats (SHR). Both treatments produced similar decrease in SBP. Amlodipine treatment reduced left ventricle, aortic and mesenteric artery weight. Marrubium treatment had a significant antihypertrophic effect in aorta only. Relaxation to acetylcholine (ACh) of mesenteric artery was improved by Marrubium but not by amlodipine treatment. These results demonstrate that, in addition to its antihypertensive effect, Marrubium water extract improved the impaired endothelial function in SHR.

  19. Genetic isolation of a blood pressure quantitative trait locus on chromosome 2 in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Vorlíček, Jaroslav; Křen, Vladimír; St. Lezin, E.; Kurtz, T. W.

    2001-01-01

    Roč. 19, č. 6 (2001), s. 1061-1064 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA305/00/1646; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : spontaneously hypertensive rat * chromosome 2 * congenic Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.210, year: 2001

  20. Dissection of Chromosome 18 Blood Pressure and Salt-Sensitivity Quantitative Trait Loci in the Spontaneously Hypertensive Rat

    Czech Academy of Sciences Publication Activity Database

    Johnson, M.D.; He, L.; Herman, D.; Wakimoto, H.; Wallace, C. A.; Zídek, Václav; Mlejnek, Petr; Musilová, Alena; Šimáková, Miroslava; Vorlíček, Jaroslav; Křen, Vladimír; Vyklický, O.; Qi, N.R.; Wang, J.; Seidman, Ch. E.; Seidman, J.; Kurtz, T. W.; Aitman, T. J.; Pravenec, Michal

    2009-01-01

    Roč. 54, č. 3 (2009), s. 639-645 ISSN 0194-911X R&D Projects: GA MŠk(CZ) 1M0520; GA MŠk(CZ) 1P05ME791; GA ČR(CZ) GA301/08/0166 Grant - others:EC(XE) LSHG-CT-2005-019015; Howard Hughes Medical Institute(US) HHMI 55005624; Transatlantic network of excellence(US) Foundation Leducq Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneously hypertensive rat * salt sensitivity * gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.614, year: 2009

  1. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A.; Podratz, P.L.; Graceli, J.B.; Abreu, G.R.

    2015-01-01

    Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women

  2. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    M.V. Borgo

    2016-01-01

    Full Text Available Drospirenone (DRSP is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2 and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87 at 12 weeks of age were randomly divided into sham operated (Sham, OVX, OVX treated with E2 (E2, and OVX treated with E2 and DRSP (E2+DRSP groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

  3. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil); Podratz, P.L.; Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil)

    2015-11-17

    Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

  4. Green asparagus (Asparagus officinalis) prevented hypertension by an inhibitory effect on angiotensin-converting enzyme activity in the kidney of spontaneously hypertensive rats.

    Science.gov (United States)

    Sanae, Matsuda; Yasuo, Aoyagi

    2013-06-12

    Green asparagus (Asparagus officinalis) is known to be rich in functional components. In the present study, spontaneously hypertensive rats (SHR) were used to clarify whether green asparagus prevents hypertension by inhibition of angiotensin-converting enzyme (ACE) activity. Six-week-old male SHR were fed a diet with (AD group) or without (ND group) 5% asparagus for 10 weeks. Systolic blood pressure (SBP) (AD: 159 ± 4.8 mmHg, ND: 192 ± 14.7 mmHg), urinary protein excretion/creatinine excretion, and ACE activity in the kidney were significantly lower in the AD group compared with the ND group. Creatinine clearance was significantly higher in the AD group compared with the ND group. In addition, ACE inhibitory activity was observed in a boiling water extract of asparagus. The ACE inhibitor purified and isolated from asparagus was identified as 2″-hydroxynicotianamine. In conclusion, 2″-hydroxynicotianamine in asparagus may be one of the factors inhibiting ACE activity in the kidney, thus preventing hypertension and preserving renal function.

  5. Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats.

    Science.gov (United States)

    Miloradović, Zoran; Mihailović-Stanojević, Nevena; Jovović, Đurđica; Ivanov, Milan; Vajić, Una J; Karanović, Danijela; Grujić Milanović, Jelica

    2015-01-01

    Limited numbers of studies include research of microvibration therapy in experimental models. We examined effects of chronic vibroacustic-microvibration treatment on haemodynamics and anti-oxidative defense in experimental hypertension. Study was performed on chronically treated hypertensive and normotensive Wistar rats. Mean arterial pressure (MAP), cardiac output (CO), renal blood flow (RBF), glomerular filtration and activity of anti-oxidative enzymes were determined after three weeks treatment. Vibroacustic treatment had no influence on MAP and CO, but RBF was increased in both groups of treated rats. Additionally, vibroacustic treatment enhanced diuresis and increased glomerular filtration in hypertensive rats. Glutathione peroxidase (GSH-Px) activity was elevated in both treated rat strains, but activity of superoxide dismutase was unchanged. We conclude that microvibration treatment doesn't ameliorate hypertension but improves renal blood supply (trough diminished renal vascular resistance), glomerular filtration, diuresis, and enhances glutathione dependent anti-oxidant defense with more important beneficials in hypertensive animals.

  6. Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.

    Science.gov (United States)

    Chen, Xin-ran; Liao, Song-jie; Ye, Lan-xiang; Gong, Qiong; Ding, Qiao; Zeng, Jin-sheng; Yu, Jian

    2014-01-16

    Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction. © 2013 Published by Elsevier B.V.

  7. Estimating right ventricular stroke work and the pulsatile work fraction in pulmonary hypertension.

    Science.gov (United States)

    Chemla, Denis; Castelain, Vincent; Zhu, Kaixian; Papelier, Yves; Creuzé, Nicolas; Hoette, Susana; Parent, Florence; Simonneau, Gérald; Humbert, Marc; Herve, Philippe

    2013-05-01

    The mean pulmonary artery pressure (mPAP) replaces mean systolic ejection pressure (msePAP) in the classic formula of right ventricular stroke work (RVSW) = (mPAP - RAP) × stroke volume, where RAP is mean right atrial pressure. Only the steady work is thus taken into account, not the pulsatile work, whereas pulmonary circulation is highly pulsatile. Our retrospective, high-fidelity pressure study tested the hypothesis that msePAP was proportional to mPAP, and looked at the implications for RVSW. Eleven patients with severe, precapillary pulmonary hypertension (PH) (six patients with idiopathic pulmonary arterial hypertension and five with chronic thromboembolic PH; mPAP = 57 ± 10 mm Hg) were studied at rest and during mild to moderate exercise. Eight non-PH control subjects were also studied at rest (mPAP = 16 ± 2 mm Hg). The msePAP was averaged from end diastole to dicrotic notch. In the full data set (53 pressure-flow points), mPAP ranged from 14 to 99.5 mm Hg, cardiac output from 2.38 to 11.1 L/min, and heart rate from 53 to 163 beats/min. There was a linear relationship between msePAP and mPAP (r² = 0.99). The msePAP matched 1.25 mPAP (bias, -0.5 ± 2.6 mm Hg). Results were similar in the resting non-PH group and in resting and the exercising PH group. This implies that the classic formula markedly underestimates RVSW and that the pulsatile work may be a variable 20% to 55% fraction of RVSW, depending on RAP and mPAP. At rest, RVSW in patients with PH was twice as high as that of the non-PH group (P work fraction was similar between the two groups (26 ± 4% vs 24 ± 1%) because of the counterbalancing effects of high RAP (11 ± 5 mm Hg vs 4 ± 2 mm Hg), which increases the fraction, and high mPAP, which decreases the fraction. Our study favored the use of an improved formula that takes into account the variable pulsatile work fraction: RVSW = (1.25 mPAP - RAP) × stroke volume. Increased RAP and increased mPAP have opposite effects on the pulsatile work

  8. The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

    Czech Academy of Sciences Publication Activity Database

    Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

    2017-01-01

    Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

  9. α2-Adrenoreceptor Constraint of Catecholamine Release and Blood Pressure Is Enhanced in Female Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Berg, Torill

    2016-01-01

    α2-adrenoceptors (α2AR) lower central sympathetic output and peripheral catecholamine release, and may therefore prevent sympathetic hyperactivity and hypertension. The α2AR are dysfunctional in male spontaneously hypertensive rats (SHR). Premenopausal females are less hypertensive than males. The purpose of this study was to test if this difference could be explained by functional α2AR in the female SHR. A 15-min tyramine-infusion was used to stimulate norepinephrine release through the re-uptake transporter, consequently preventing re-uptake. Presynaptic control of vesicular release will therefore be reflected as differences in overflow to plasma. The surgical trauma activates secretion of epinephrine, also subjected to α2AR auto-inhibition. Blood pressure was monitored through a femoral artery catheter and cardiac output by ascending aorta flow in 12-14 weeks-old (early hypertension) SHR and normotensive rats (WKY). Total peripheral vascular resistance (TPR) was calculated. Female SHR, unlike male, were close to normotensive. Pre-treatment with none-selective (clonidine) or non-A-selective (ST-91) α2AR agonist reduced, and none-selective α2AR antagonist (L-659,066) increased tyramine-induced norepinephrine overflow in female WKY and SHR. L-659,066 also increased secretion of epinephrine. The L-659,066-induced increase in catecholamine release was further enhanced by additional pre-treatment with ST-91 or angiotensin AT1 receptor antagonist (losartan) in SHR only. L-659,066 eliminated the tyramine-induced rise in TPR in both strains in female rats. α2AR-mediated control of catecholamine release and vascular tension was therefore functional in female SHR, unlike that previously observed in male SHR. Functional α2AR is likely to have a protective function and may explain the lack of hypertension in the young female SHR.

  10. α2-ADRENOCEPTOR CONSTRAINT OF CATECHOLAMINE RELEASE AND BLOOD PRESSURE IS ENHANCED IN FEMALE SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Torill eBerg

    2016-03-01

    Full Text Available α2-adrenoceptors (α2AR lower central sympathetic output and peripheral catecholamine release, and may therefore prevent sympathetic hyperactivity and hypertension. The α2AR are dysfunctional in male spontaneously hypertensive rats (SHR. Premenopausal females are less hypertensive than males. The purpose of this study was to test if this difference could be explained by functional α2AR in the female SHR. A 15-min tyramine-infusion was used to stimulate norepinephrine release through the re-uptake transporter, consequently preventing re-uptake. Presynaptic control of vesicular release will therefore be reflected as differences in overflow to plasma. The surgical trauma activates secretion of epinephrine, also subjected to α2AR auto-inhibition. Blood pressure was monitored through a femoral artery catheter and cardiac output by ascending aorta flow in 12-14 weeks-old (early hypertension SHR and normotensive rats (WKY. Total peripheral vascular resistance (TPR was calculated. Female SHR, unlike male, were close to normotensive. Pre-treatment with none-selective (clonidine or non-A-selective (ST-91 α2AR agonist reduced, and none-selective α2AR antagonist (L-659,066 increased tyramine-induced norepinephrine overflow in female and WKY and SHR. L-659,066 also increased secretion of epinephrine. The L-659,066-induced increase in catecholamine release was further enhanced by additional pre-treatment with ST-91 or angiotensin AT1 receptor antagonist (losartan in SHR only. L-659,066 eliminated the tyramine-induced rise in TPR in both strains in female rats. Conclusion: α2AR-mediated control of catecholamine release and vascular tension was therefore functional in female SHR, unlike that previously observed in male SHR. Functional α2AR is likely to have a protective function and may explain the lack of hypertension in the young female SHR.

  11. Antioxidant and Antihypertensive Effects of a Chemically Defined Fraction of Syrah Red Wine on Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Figueiredo, Eugênia Abrantes de; Alves, Naiane Ferraz Bandeira; Monteiro, Matheus Morais de Oliveira; Cavalcanti, Clenia de Oliveira; Silva, Tania Maria Sarmento da; Silva, Telma Maria Guedes da; Braga, Valdir de Andrade; Oliveira, Eduardo de Jesus

    2017-06-03

    A particularly phenolic-rich fraction extracted from red wine from the São Francisco valley (Northeastern Brazil) was chemically characterized and its hypotensive and antioxidant effects on spontaneously hypertensive rats were studied both in vitro and in vivo. The liquid-liquid pH dependent fractionation scheme afforded a fraction with high content of bioactive phenolics such as flavonols, flavonol glycosides, phenolic acids and anthocyanins, whose identities were confirmed by liquid chromatography coupled to mass spectrometry analysis. Pretreatment of spontaneously hypertensive rats with this wine fraction at doses of 50 and 100 mg/kg by gavage. for 15 days was able to decrease mean arterial pressure and heart rate as well as decrease serum lipid peroxidation. The fraction at concentrations of 0.01-1000 µg/mL induced concentration-dependent relaxation of isolated rat superior mesenteric artery rings pre-contracted with phenylephrine and this effect was not attenuated by endothelium removal. Our results demonstrate it is possible for phenolic constituents of red wine that are orally bioavailable to exert in vivo hypotensive and antioxidant effects on intact endothelial function.

  12. Antioxidant and Antihypertensive Effects of a Chemically Defined Fraction of Syrah Red Wine on Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Eugênia Abrantes de Figueiredo

    2017-06-01

    Full Text Available A particularly phenolic-rich fraction extracted from red wine from the São Francisco valley (Northeastern Brazil was chemically characterized and its hypotensive and antioxidant effects on spontaneously hypertensive rats were studied both in vitro and in vivo. The liquid-liquid pH dependent fractionation scheme afforded a fraction with high content of bioactive phenolics such as flavonols, flavonol glycosides, phenolic acids and anthocyanins, whose identities were confirmed by liquid chromatography coupled to mass spectrometry analysis. Pretreatment of spontaneously hypertensive rats with this wine fraction at doses of 50 and 100 mg/kg by gavage. for 15 days was able to decrease mean arterial pressure and heart rate as well as decrease serum lipid peroxidation. The fraction at concentrations of 0.01–1000 µg/mL induced concentration-dependent relaxation of isolated rat superior mesenteric artery rings pre-contracted with phenylephrine and this effect was not attenuated by endothelium removal. Our results demonstrate it is possible for phenolic constituents of red wine that are orally bioavailable to exert in vivo hypotensive and antioxidant effects on intact endothelial function.

  13. Effects of atorvastatin on calcium-regulating proteins: a possible mechanism to repair cardiac dysfunction in spontaneously hypertensive rats.

    Science.gov (United States)

    Yao, Lei; Chen, Guo-Ping; Lu, Xian; Zheng, Liang-Rong; Mou, Yun; Hu, Shen-Jiang

    2009-05-01

    Previous clinical and experimental studies have demonstrated that statins, the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can improve left ventricular function in damaged hearts. Also, the normal expression of Ca(2+) regulatory proteins is critical for efficient myocardial function. However, it is still unclear whether the beneficial effect of statins on cardiac function is associated with alterations of Ca(2+) regulatory proteins. In this study, we investigated the effect of atorvastatin on cardiac function in spontaneously hypertensive rats (SHRs), focusing in particular on its impact on the expression of sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase (SERCA2a), phospholamban (PLB) and its phosphorylated form (phosphorylated PLB), all of which are Ca(2+) regulatory proteins in myocardium. SHRs showed decreases in gene expression of SERCA2a and phosphorylated PLB, and reduction in SERCA activity in the left ventricular myocardium, as well as reduced cardiac function, compared to age-matched Wistar Kyoto rats (WKYs). Furthermore, we showed that in SHRs atorvastatin preserved cardiac dysfunction accompanied by positive alterations in calcium regulatory proteins, with up-regulation in expression of SERCA2a and phosphorylated PLB, and with improvement of SERCA activity. Thus, atorvastatin has positive effects on calcium regulatory proteins, which may be one of the mechanisms of the beneficial effect of statins on cardiac function in spontaneously hypertensive rats.

  14. Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats

    Science.gov (United States)

    Background: Previous studies provided compelling evidences for particulate matter (PM) associated cardiovascular health effects. Elderly individuals, particularly those with preexisting conditions like hypertension are regarded to be vulnerable. Experimental data are warranted to...

  15. Sleeping over a sleep disorder - Awareness of obstructive sleep apnoea as a modifiable risk factor for hypertension and stroke: A survey among health care professionals and medical students

    Directory of Open Access Journals (Sweden)

    Sushma Sharma

    2013-01-01

    Full Text Available Background: Obstructive sleep apnoea (OSA syndrome is an established and modifiable but under recognized risk factor for common disorders like stroke and hypertension. Objective: To assess awareness level of health care practitioners and medical students about OSA as a risk factor for stroke and hypertension. Methods: Questionnaire based survey with multiple response type and fill in the blanks type questions. The data was compiled and analyzed using SPSS version 19. Results: 180 participants completed the survey questionnaire. Only 24 (13.3% identified OSA as a reversible risk factor for ischemic stroke. 11 (6% participants only could answer OSA as an identified risk factor for hypertension as per Seventh Joint National Committee report. Poor awareness extended over all categories of participants (medical students, trained doctors and nursing staff . Conclusion: This study reveals dismal level of awareness, among health professionals and medical students, about OSA being an established and modifiable risk factor for hypertension and ischemic stroke.

  16. Cross-fostering does not alter the neurochemistry or behavior of spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Russell Vivienne A

    2009-06-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a highly heritable developmental disorder resulting from complex gene-gene and gene-environment interactions. The most widely used animal model, the spontaneously hypertensive rat (SHR, displays the major symptoms of ADHD (deficits in attention, impulsivity and hyperactivity and has a disturbance in the noradrenergic system when compared to control Wistar-Kyoto rats (WKY. The aim of the present study was to determine whether the ADHD-like characteristics of SHR were purely genetically determined or dependent on the gene-environment interaction provided by the SHR dam. Methods SHR/NCrl (Charles River, USA, WKY/NCrl (Charles River, USA and Sprague Dawley rats (SD/Hsd, Harlan, UK were bred at the University of Cape Town. Rat pups were cross-fostered on postnatal day 2 (PND 2. Control rats remained with their birth mothers to serve as a reference for their particular strain phenotype. Behavior in the open-field and the elevated-plus maze was assessed between PND 29 and 33. Two days later, rats were decapitated and glutamate-stimulated release of [3H]norepinephrine was determined in prefrontal cortex and hippocampal slices. Results There was no significant effect of "strain of dam" but there was a significant effect of "pup strain" on all parameters investigated. SHR pups travelled a greater distance in the open field, spent a longer period of time in the inner zone and entered the inner zone of the open-field more frequently than SD or WKY. SD were more active than WKY in the open-field. WKY took longer to enter the inner zone than SHR or SD. In the elevated-plus maze, SHR spent less time in the closed arms, more time in the open arms and entered the open arms more frequently than SD or WKY. There was no difference between WKY and SD behavior in the elevated-plus maze. SHR released significantly more [3H]norepinephrine in response to glutamate than SD or WKY in both hippocampus

  17. A CLA enriched diet improves organ damage associated with the metabolic syndrome in spontaneous hypertensive rats

    Directory of Open Access Journals (Sweden)

    Soto-Rodríguez, Ida

    2011-03-01

    Full Text Available The purpose of this study was to provide evidence that dietary CLA can prevent the pathogenesis of metabolic syndrome in tissue structure, suggesting potential benefits in the onset of this syndrome. Wistar male spontaneous hypertensive rats (SHR, were classified into two groups that were fed a standard diet for eight weeks: one with 7.5% sunflower oil (V-SHR group, and the other with 6% sunflower oil and 1.5% CLA (CLA-SHR group. A control healthy group consisted of Kyoto-Wistar male rats fed the standard diet with 7.5% sunflower oil. The animals were sacrificed, and sections of liver, kidneys and aorta were fixed in 10% formaldehyde, and then stained with Hematoxylin and Eosin. Only in the V-SHR group, the stain of the aorta indicated irregular endothelial morphology; liver parenchyma was characterized by an infiltration of inflammatory neutrophils, fibrosis, thickening of the portal vein epithelium, hepatocyte hyperplasia and steatosis. The renal tissue of this group evidenced hyperplasia in the cells of the endothelial of Bowman´s capsule. Abnormal histological changes were not observed in either the control group or the rats fed with CLA, suggesting a protective role of CLA in the onset of metabolic syndrome.

    El objetivo del presente estudio fue proporcionar evidencia que el CLA dietario puede evitar la patogénesis del síndrome metabólico en la estructura tisular, lo que sugiere beneficios potenciales en el desarrollo de este síndrome. Dos grupos de ratas Wistar macho espontáneamente hipertensas (SHR fueron alimentadas con una dieta normal por 8 semanas: una dieta contenía 7.5% de aceite de girasol (grupo VSHR, y el otro contenía 6% de aceite de girasol y 1.5% de CLA (grupo CLA-SHR. A un grupo testigo sano de ratas macho Kyoto-Wistar les fue proporcionada una dieta normal con 7.5% de aceite de girasol. Los animales fueron sacrificados y se tomaron secciones de hígado, riñones y aorta, las cuales fueron fijadas en formaldeh

  18. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Directory of Open Access Journals (Sweden)

    Xavier eLópez-Gil

    2014-07-01

    Full Text Available The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

  19. Sleeping over a sleep disorder - Awareness of obstructive sleep apnoea as a modifiable risk factor for hypertension and stroke: A survey among health care professionals and medical students

    OpenAIRE

    Sharma, Sushma; Srijithesh, P. R.

    2013-01-01

    Background: Obstructive sleep apnoea (OSA) syndrome is an established and modifiable but under recognized risk factor for common disorders like stroke and hypertension. Objective: To assess awareness level of health care practitioners and medical students about OSA as a risk factor for stroke and hypertension. Methods: Questionnaire based survey with multiple response type and fill in the blanks type questions. The data was compiled and analyzed using SPSS version 19. Results: 180 participant...

  20. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Steiner, Thorsten; Al-Shahi Salman, Rustam; Beer, Ronnie

    2014-01-01

    BACKGROUND: Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has...

  1. Effect of the Antihypertensive Drug Enalapril on Oxidative Stress Markers and Antioxidant Enzymes in Kidney of Spontaneously Hypertensive Rat

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    G. Chandran

    2014-01-01

    Full Text Available Oxidative stress has been suggested to play a role in hypertension and hypertension induced organ damage. This study examined the effect of enalapril, an antihypertensive drug, on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat (SHR and Nω -nitro-L-arginine methyl ester (L-NAME administered SHR. Male rats were divided into four groups (SHR, SHR+enalapril, SHR+L-NAME, and SHR+enalapril+L-NAME. Enalapril (30 mg kg−1 day−1 was administered from week 4 to week 28 and L-NAME (25 mg kg−1 day−1 was administered from week 16 to week 28 in drinking water. Systolic blood pressure (SBP was measured during the experimental period. At the end of experimental periods, rats were sacrificed; urine, blood, and kidneys were collected for the assessment of creatinine clearance, total protein, total antioxidant status (TAS, thiobarbituric acid reactive substances (TBARS, superoxide dismutase (SOD, and catalase (CAT, as well as histopathological examination. Enalapril treatment significantly enhanced the renal TAS level (P<0.001 and SOD activity (P<0.001, reduced the TBARS levels (P<0.001, and also prevented the renal dysfunction and histopathological changes. The results indicate that, besides its hypotensive and renoprotective effects, enalapril treatment also diminishes oxidative stress in the kidneys of both the SHR and SHR+L-NAME groups.

  2. Antihypertensive and Antihypertrophic Effects of Acupuncture at PC6 Acupoints in Spontaneously Hypertensive Rats and the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Juan-Juan Xin

    2017-01-01

    Full Text Available The aim of this work is to investigate the effect of electroacupuncture (EA at PC6 on the hypertension and myocardial hypertrophy in spontaneously hypertensive rats (SHRs. Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA group with WKY rats as normal control. EA was applied once a day in 8 consecutive weeks. The blood pressure (BP, cardiac function, and hypertrophy as well as the underlying mechanisms were investigated. After EA treatment, the enhanced BP in SHR + EA group was significantly lower compared to both the period before EA and model group. Echocardiographic, morphological studies showed that the enhanced left ventricular anterior and posterior wall end-diastolic (LVAWd and LVPWd thickness, diameters and cross-sectional area (CSA of cardiac myocyte, as well as the ratio of heart weight to body weight (HW/BW, were markedly diminished in SHR + EA group, while the reduced left ventricular ejection fraction, left ventricular short axis fraction shortening, and E/A ratio were significantly ameliorated. The levels of Angiotensin-converting enzyme (ACE and Angiotensin II Type 1 and 2 receptors (AT1R, AT2R in SHRs were also significantly attenuated by EA. The results suggest that EA at bilateral PC6 could arrest the hypertension development and ameliorate the cardiac hypertrophy and malfunction in SHRs, which might be mediated by the regulation of ACE, AT1R, and AT2R.

  3. Long-term antihypertensive effects of far-infrared ray irradiated from wooden board in spontaneously hypertensive rats.

    Science.gov (United States)

    Lin, Chien-Tsong; Lin, Ming-Ju; Chen, Yung-Pin; Lee, Ko-Chao; Huang, Kuo-Chin; Chang, Shun-Fu; Chen, Cheng-Nan

    2016-02-08

    Far-infrared ray (FIR) has been widely used in promoting health and has been shown to exert beneficial effects in vascular function. The non-thermal effect of FIR has been found to play a significant role in the protective effect on some vascular-related diseases, but its protective effects and use against hypertension have not been clearly presented. In the present study, by using a wooden board coated with FIR-irradiated materials, we evaluated the long-term antihypertensive effect on spontaneously hypertensive rats (SHRs) in the environment in contact with the FIR-irradiated wooden board. SHRs were placed on the wooden board with or without FIR radiation for 4 weeks. The systolic blood pressure (BP) of SHRs undergoing different treatments was measured weekly using a tail-cuff method. FIR radiation significantly reduced the systolic BP of the SHRs along with a decreasing plasma level of angiotensin II and an increasing plasma level of bradykinin. In addition, long-term contact of FIR did not significantly affect the BP in normotensive Wistar Kyoto rats (WKYs). Our results provided the evidence based on which FIR radiation could be considered an effective non-pharmacological choice for preventing hypertension.

  4. Effects of hydrochlorothiazide on oxidative stress and pulse pressure in hypertensive patients with chronic stroke: the EMINENT study.

    Science.gov (United States)

    Nakane, Hiroshi; Kamouchi, Masahiro; Hata, Jun; Ibayashi, Setsuro; Kusuda, Kenji; Omae, Tsuyoshi; Nagao, Tetsuhiko; Ago, Tetsuro; Kitazono, Takanari

    2015-01-01

    Thiazide diuretics are reported to have antioxidant effects and reduce pulse pressure (PP). The aim of this study was to elucidate whether hydrochlorothiazide additionally exerts such effects in stroke patients under treatment with losartan. This study was an open-label, randomized, multicenter study. Patients with a history of chronic stroke and treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors for essential hypertension were enrolled. Fifty-five hypertensive patients were randomly assigned to two groups: those further treated with hydrochlorothiazide and those further treated with non-diuretic antihypertensive drugs. Both groups showed a significant decrease in PP over six months (hydrochlorothiazide group: 67±12 mmHg to 58±12, phydrochlorothiazide treatment did not provide any additional benefits over non-diuretic antihypertensive drugs in terms of antioxidant effects or reducing PP.

  5. Time-Dependent Effects of Training on Cardiovascular Control in Spontaneously Hypertensive Rats: Role for Brain Oxidative Stress and Inflammation and Baroreflex Sensitivity

    OpenAIRE

    Masson, Gustavo S.; Costa, Tassia S. R.; Yshii, Lidia; Fernandes, Denise C.; Soares, Pedro Paulo Silva; Laurindo, Francisco R.; Scavone, Cristoforo; Michelini, Lisete C.

    2014-01-01

    Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in traine...

  6. Angiotensin Type 2 Receptor Stimulation Increases Renal Function in Female, but Not Male, Spontaneously Hypertensive Rats

    DEFF Research Database (Denmark)

    Hilliard, Lucinda M; Chow, Charis L E; Mirabito, Katrina M

    2014-01-01

    in female hypertensive rats (PTreatmentarterial pressure. For example, at 300 ng/kg per minute of compound 21, renal blood flow increased by 14.3±1.8% from baseline. Furthermore, at 300 ng/kg per minute of compound 21, a significant increase in urinary sodium excretion...... vasodilatation and sodium excretion without concomitant alterations in glomerular filtration rate in female hypertensive rats. Chronic studies of AT2R agonist therapy on renal function and arterial pressure in hypertensive states are now required to establish the suitability of AT2R as a therapeutic target......Accumulating evidence suggests that the protective pathways of the renin-angiotensin system are enhanced in women, including the angiotensin type 2 receptor (AT2R), which mediates vasodilatory and natriuretic effects. To provide insight into the sex-specific ability of pharmacological AT2R...

  7. Effects of a hot-water extract of porcini (Boletus aestivalis) mushrooms on the blood pressure and heart rate of spontaneously hypertensive rats.

    Science.gov (United States)

    Midoh, Naoki; Miyazawa, Noriko; Eguchi, Fumio

    2013-01-01

    The repeated once-daily oral administration of a hot-water extract of porcini, Boletus aestivalis, mushrooms (WEP) to spontaneously hypertensive rats (SHR) for 18 weeks decreased the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. The WEP administration also decreased blood urea nitrogen (BUN), creatinine (Cre), and triglyceride (TG), and increased high-density lipoprotein-cholesterol (HDL-C) in the blood, suggesting that WEP improved the status of hypertension, as well as the high heart rate and metabolic abnormalities involved in hypertension.

  8. The participation of brain NO synthase in blood pressure control of adult spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Hojná, Silvie; Kadlecová, Michaela; Dobešová, Zdenka; Valoušková, V.; Zicha, Josef; Kuneš, Jaroslav

    2007-01-01

    Roč. 297, 1-2 (2007), s. 21-29 ISSN 0300-8177 R&D Projects: GA MZd NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : NOS * genetic hypertension * sympathetic vasoconstriction Subject RIV: ED - Physiology Impact factor: 1.707, year: 2007

  9. THE PREVALENCE OF ARTERIAL HYPERTENSION AS ONE OF THE LEADING FACTORS OF THE STROKE RISK IN THE MOSCOW REGION ON THE EXAMPLE OF THE SMALL REGIONAL SETTLEMENT

    Directory of Open Access Journals (Sweden)

    V. V. Kоzyaikin

    2013-01-01

    Full Text Available Analysis of the clinical-and-epidemiological parameters of the stroke was carried out and the prevalence of arterial hypertension was studied as one of the leading factors of stroke development among the residents of the small regional settlement of the Moscow Region. The epidemiological data obtained are indicative of the high stroke morbidity. A significant prevalence of the arterial hypertension was found in the population studied as well as an insufficient control and low understanding by patients of the necessity of regular taking antihypertensive drugs.

  10. Addition of an Enzymatic Hydrolysate of Bovine Globulins to Bread and Determination of Hypotensive Effects in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Lafarga, Tomas; Gallagher, Eimear; Aluko, Rotimi E; Auty, Mark A E; Hayes, Maria

    2016-03-02

    The aim of this study was to develop bread containing a papain hydrolysate of bovine α- and β-globulins (GPH) with in vitro and in vivo antihypertensive activities. The physical characteristics of the formulated bread were assessed over a six day period and results suggested that the overall quality and acceptance of bread was not affected by the inclusion of GPH at a concentration of 4% (w/w). Bright field light microscopy and confocal scanning laser microscopy images were used to visualize the main ingredients of the bread. In addition, the antihypertensive activity of the bread was assessed in spontaneously hypertensive rats (SHRs) over a 24 h period where a maximum significant decrease in systolic blood pressure of 36.2 ± 1.9 mmHg was observed 8 h after oral administration. Results demonstrate that the antihypertensive activity of GPH was resistant to the baking process and shows potential for use as a functional antihypertensive ingredient.

  11. CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene expression profile analysis

    Czech Academy of Sciences Publication Activity Database

    Neckář, Jan; Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Seidman, J. G.; Seidman, Ch.; Kazdová, L.; Klevstig, M.; Novák, F.; Vecka, M.; Papoušek, František; Houštěk, Josef; Drahota, Zdeněk; Kurtz, T. W.; Kolář, František; Pravenec, Michal

    2012-01-01

    Roč. 44, č. 2 (2012), s. 173-182 ISSN 1094-8341 R&D Projects: GA MŠk(CZ) ME08006; GA MŠk(CZ) 1M0520; GA MŠk(CZ) OC08017; GA MŠk(CZ) 1M0510; GA MZd(CZ) NR9359; GA MZd(CZ) NR9387; GA MZd(CZ) NS9757; GA MZd(CZ) NS10504; GA AV ČR(CZ) IAA500110805; GA AV ČR(CZ) IAAX01110901; GA AV ČR(CZ) KAN200520703; GA ČR(CZ) GD305/08/H037; GA ČR GAP301/10/0756; GA MŠk 7E10067 Institutional research plan: CEZ:AV0Z50110509 Keywords : Cd36 * spontaneously hypertensive rat * arrhythmias * infarct size * gene expression profiles Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.806, year: 2012

  12. Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis.

    Science.gov (United States)

    Carr, Susan J; Wang, Xia; Olavarria, Veronica V; Lavados, Pablo M; Rodriguez, Jorge A; Kim, Jong S; Lee, Tsong-Hai; Lindley, Richard I; Pontes-Neto, Octavio M; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K; Woodward, Mark; Chalmers, John; Anderson, Craig S; Robinson, Thompson G

    2017-09-01

    Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, 90 mL/min per 1.73 m 2 ), those with severe RD (stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.70; P =0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P =0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades. RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616. © 2017 American Heart Association, Inc.

  13. Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

    Czech Academy of Sciences Publication Activity Database

    Polidarová, Lenka; Sládek, Martin; Nováková, Marta; Parkanová, Daniela; Sumová, Alena

    2013-01-01

    Roč. 8, č. 9 (2013), e75690 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP303/11/0668 Institutional support: RVO:67985823 Keywords : circadian * clock gene * metabolism * liver * feeding regime * Bmal2 * spontaneously hypertensive rat Subject RIV: ED - Physiology Impact factor: 3.534, year: 2013

  14. Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Trnovská, J.; Kazdová, L.; Pravenec, Michal

    2014-01-01

    Roč. 63, č. 5 (2014), s. 587-590 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12061 Institutional support: RVO:67985823 Keywords : sterol regulatory element binding protein 2 * transgenic * spontaneously hypertensive rat * lipid metabolism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  15. Renoprotective Effects of Melatonin in Young Spontaneously Hypertensive Rats with L-NAME

    Directory of Open Access Journals (Sweden)

    Ming-Chou Cheng

    2014-06-01

    Conclusion: Our results indicated that L-NAME/SHR is a useful model for hypertensive nephrosclerosis in young rats. The blood pressure-lowering and renoprotective effects of melatonin is due to increases of DDAH activity, decreases of ADMA, and reduction of oxidative stress in L-NAME-treated SHR kidney. Specific therapy targeting the DDAH–ADMA pathway may be a promising approach to slowing chronic kidney disease progression in children.

  16. Placental 11beta-hydroxysteroid dehydrogenase in Dahl and spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Mazancová, Karla; Mikšík, Ivan; Kuneš, Jaroslav; Pácha, Jiří

    2003-01-01

    Roč. 16, 5, Pt 1 (2003), s. 401-406 ISSN 0895-7061 R&D Projects: GA ČR GA306/99/0210 Grant - others:GA UK(CZ) 44/2002/C/2.LF Institutional research plan: CEZ:AV0Z5011922 Keywords : 11beta-hydroxysteroid dehydrogenase * placenta * rat hypertension Subject RIV: ED - Physiology Impact factor: 3.103, year: 2003

  17. Short-term hypertension management in community is associated with long-term risk of stroke and total death in China: A community controlled trial.

    Science.gov (United States)

    Wang, Zengwu; Hao, Guang; Wang, Xin; Wang, Wen; Chen, Weiwei; Zhu, Manlu

    2016-11-01

    It is not fully clear whether the effect of short-term management in community can reduce the long-term risk of stroke OBJECTIVES:: To evaluate whether short-term hypertension management is associated with long-term incidence of stroke and total death in community health centers in China. Community controlled trail. Six community health centers (4 active, 2 control) in China, patients with hypertension. Patients were treated with normally therapy method. Patients were treated oriented by the Guideline for hypertension management. Two centers (Hebei and Zhejiang) from the Hypertension Control in Community (HCC) Project, which was conducted from 2005 to 2008, were randomly selected for this study. Four thousand hypertensive patients from these centers, who were under management for one year in the baseline, were followed up in 2013. The electronic health record system (2005-2008) was used to identify 2000 hypertensive patients, who were not included in HCC but lived in comparable community health center in the same province, as the control group. All baseline and follow-up data were collected using standardized questionnaires for stroke outcomes. Stroke. Of the 6000 participants, 3787 (63.1%) were eligible for analysis. At the time of follow-up, the average BP was kept in the lower level than that in baseline, and the control rate was 59.3%. After propensity-score matching, 110 strokes (2.0% vs 4.6%) and 141 deaths (1.4% vs 3.8%) were noted in the matched intervention and control groups (1078 pairs), respectively. Patients in the intervention group were less likely to experience a stroke or die than those in the control group (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.26-0.62, P stroke in hypertensive patients.

  18. Reduced capacity of autonomic and baroreflex control associated with sleep pattern in spontaneously hypertensive rats with a nondipping profile.

    Science.gov (United States)

    Chen, Chieh-Wen; Kuo, Terry B J; Chen, Chun-Yu; Yang, Cheryl C H

    2017-03-01

    Ambulatory blood pressure (BP) monitoring with a lack of nocturnal BP fall (BP nondipping) has been reported to be more prevalent among hypertensive populations and is a risk factor for cardiovascular disease than in patients with dipping pattern. However, its underlying mechanism is not fully understood. This study hypothesized that spontaneously hypertensive rats (SHRs) with a nondipping profile have an exaggerated disruption of both autonomic functioning and sleep compared with Wistar-Kyoto rats (WKYs) with a nondipping profile. Continuous power spectral analysis of electroencephalogram, electromyogram, and cardiovascular variability was performed in WKYs and SHRs over 24 h. BP dipping was assessed as the percentage decline in SBP from dark active waking to light quiet sleep (lQS). According to the human definition of BP dipping (10%), we divided WKYs and SHRs into dipper and nondipper groups individually. Of the four groups, both parasympathetic activity and baroreflex sensitivity in sleep were the lowest in the SHR nondippers. Compared with the WKY nondippers, the SHR nondippers spent more time awake and less time asleep during the light period and the opposite during the dark period. Moreover, they showed more interruptions and a lower delta power percentage of lQS. Correlation analysis revealed that baroreflex sensitivity during lQS was correlated with the BP dipping percentage in SHRs. SHR nondippers exhibit poor sleep quality and impaired autonomic functioning to a greater degree than do SHR dippers and WKY nondippers, which may account for a higher cardiovascular risk in this population.

  19. Morphometric analysis of the phrenic nerve in male and female Wistar-Kyoto (WKY and spontaneously hypertensive rats (SHR

    Directory of Open Access Journals (Sweden)

    A.R. Rodrigues

    2011-06-01

    Full Text Available Ventilatory differences between rat strains and genders have been described but the morphology of the phrenic nerve has not been investigated in spontaneously hypertensive (SHR and normotensive Wistar-Kyoto (WKY rats. A descriptive and morphometric study of the phrenic nerves of male (N = 8 and female (N = 9 SHR, and male (N = 5 and female (N = 6 WKY is presented. After arterial pressure and heart rate recordings, the phrenic nerves of 20-week-old animals were prepared for epoxy resin embedding and light microscopy. Morphometric analysis performed with the aid of computer software that took into consideration the fascicle area and diameter, as well as myelinated fiber profile and Schwann cell nucleus number per area. Phrenic nerves were generally larger in males than in females on both strains but larger in WKY compared to SHR for both genders. Myelinated fiber numbers (male SHR = 228 ± 13; female SHR = 258 ± 4; male WKY = 382 ± 23; female WKY = 442 ± 11 for proximal right segments and density (N/mm²; male SHR = 7048 ± 537; female SHR = 10355 ± 359; male WKY = 9457 ± 1437; female WKY = 14351 ± 1448 for proximal right segments were significantly larger in females of both groups and remarkably larger in WKY than SHR for both genders. Strain and gender differences in phrenic nerve myelinated fiber number are described for the first time in this experimental model of hypertension, indicating the need for thorough functional studies of this nerve in male and female SHR.

  20. Differing chemical compositions of three teas may explain their different effects on acute blood pressure in spontaneously hypertensive rats.

    Science.gov (United States)

    Li, Shan-Bing; Li, Yi-Fang; Mao, Zhong-Fu; Hu, Hui-Hua; Ouyang, Shu-Hua; Wu, Yan-Ping; Tsoi, Bun; Gong, Pin; Kurihara, Hiroshi; He, Rong-Rong

    2015-04-01

    Heavy tea consumption is suggested to be unsuitable for hypertensive people. However, the bioactive substances in different varieties of tea leaves are very different. This study compares the effects of three Chinese teas - C. sinensis, C. ptilophylla and C. assamica var. kucha - on blood pressure (BP) and heart rate in spontaneously hypertensive rats (SHRs). Intragastric administration of C. sinensis extract led to an acute increase in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate in SHRs. However, C. ptilophylla and C. assamica var. kucha exerted no obvious influences on SBP, DBP or heart rate. Similar to the extract of C. sinensis, intragastric administration of caffeine also led to an acute increase in BP and heart rate in SHRs. In contrast, theobromine and theacrine - purine alkaloids predominantly contained in C. ptilophylla and C. assamica var. kucha, respectively - had no pressor effects. The effect of caffeine on BP was related to the regulation of plasma epinephrine and norepinephrine levels in SHRs. The different effects of C. sinensis, C. ptilophylla and C. assamica var. kucha on BP might be explained, at least partially, by the differences in the varieties and contents of purine alkaloids. © 2014 Society of Chemical Industry.

  1. Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Foster Martyn

    2009-11-01

    Full Text Available Abstract Background Continuous exposure to tobacco smoke (TS is a key cause of chronic obstructive pulmonary disease (COPD, a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD. Methods SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry. Results TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion. Conclusion This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.

  2. Antihypertensive potential and mechanism of action of astaxanthin: II. Vascular reactivity and hemorheology in spontaneously hypertensive rats.

    Science.gov (United States)

    Hussein, Ghazi; Goto, Hirozo; Oda, Shinobu; Iguchi, Tomomi; Sankawa, Ushio; Matsumoto, Kinzo; Watanabe, Hiroshi

    2005-06-01

    The current study was designed to determine the effects of a dietary astaxanthin (ASX-O) on vascular reactivity in spontaneously hypertensive rats (SHR), in order to verify its antihypertensive action mechanism. We evaluated contractions induced by phenylephrine (Phe), angiotensin II (Ang II) and the xanthine/xanthine oxidase (Xan/XOD) system, and relaxations induced by sodium nitroprusside (SNP) as well as endothelium-dependent relaxations mediated by acetylcholine (ACh) in thoracic aorta of the SHR, with and without ASX-O intervention. We also investigated the effects of ASX-O on blood rheology using a microchannel array system. In this study, ASX-O showed a significant modulatory effect on nitric oxide (NO)-induced vasorelaxation by the NO-donor SNP (pASX-O (pASX-O also demonstrated significant hemorheological effect by decreasing the microchannel transit time of whole blood. In conclusion, the results suggest that ASX-O may act in modulating the blood fluidity in hypertension, and that the antihypertensive effects of ASX-O may be exerted through mechanisms including normalization of the sensitivity of the adrenoceptor sympathetic pathway, particularly [alpha]-adrenoceptors, and by restoration of the vascular tone through attenuation of the Ang II- and reactive oxygen species (ROS)-induced vasoconstriction.

  3. Excess salt increases infarct size produced by photothrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Hiroshi Yao

    Full Text Available Cerebral circulation is known to be vulnerable to high salt loading. However, no study has investigated the effects of excess salt on focal ischemic brain injury. After 14 days of salt loading (0.9% saline or water, spontaneously hypertensive rats (SHR and normotensive Wistar-Kyoto rats (WKY were subjected to photothrombotic middle cerebral artery occlusion (MCAO, and infarct volume was determined at 48 h after MCAO: albumin and hemoglobin contents in discrete brain regions were also determined in SHR. Salt loading did not affect blood pressure levels in SHR and WKY. After MCAO, regional cerebral blood flow (CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning, was more steeply decreased in the salt-loaded group than in the control group. In SHR/Izm, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p = 0.002, while the extents of blood-brain barrier disruption (brain albumin and hemoglobin levels were not affected by excess salt. In WKY, salt loading did not significantly increase infarct size. These results show the detrimental effects of salt loading on intra-ischemic CBF and subsequent brain infarction produced by phototrhombotic MCAO in hypertensive rats.

  4. Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat

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    Bolanle C. Akinwumi

    2017-02-01

    Full Text Available Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK, and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids? do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function,and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy.

  5. Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats.

    Science.gov (United States)

    Ngo, Dai-Hung; Kang, Kyong-Hwa; Ryu, BoMi; Vo, Thanh-Sang; Jung, Won-Kyo; Byun, Hee-Guk; Kim, Se-Kwon

    2015-05-01

    The aim of this study was to investigate antihypertensive effect of bioactive peptides from skate (Okamejei kenojei) skin gelatin. The Alcalase/protease gelatin hydrolysate below 1 kDa (SAP) exhibited the highest angiotensin-I converting enzyme (ACE) inhibition compared to other hydrolysates. SAP can decrease systolic blood pressure significantly in spontaneously hypertensive rats. SAP inhibited vasoconstriction via PPAR-γ expression, activation and phosphorylation of eNOS in lungs. Moreover, the expression levels of endothelin-1, RhoA, α-smooth muscle actin, cleaved caspase 3 and MAPK were decreased by SAP in lungs. Vascularity, muscularization and cellular proliferation in lungs were detected by immunohistochemical staining. Finally, two purified peptides (LGPLGHQ, 720Da and MVGSAPGVL, 829Da) showed potent ACE inhibition with IC50 values of 4.22 and 3.09 μM, respectively. These results indicate that bioactive peptides isolated from skate skin gelatin may serve as candidates against hypertension and could be used as functional food ingredients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Long-term ingestion of Hibiscus sabdariffa calyx extract enhances myocardial capillarization in the spontaneously hypertensive rat.

    Science.gov (United States)

    Inuwa, Ibrahim; Ali, Badreldin H; Al-Lawati, Intisar; Beegam, Sumaya; Ziada, Amal; Blunden, Gerald

    2012-05-01

    The effects of Hibiscus sabdariffa (HS) in lowering blood pressure in human and animal hypertension have been documented. This study investigated the effect of the water extract of the dried calyx of HS and Hibiscus anthocyanins (HAs) on left ventricular myocardial capillary length and surface area in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were divided into eight groups (six rats in each group). Three groups were given three doses; 10%, 15% and 20% of the water extract of HS in lieu of drinking water for 10 consecutive weeks (HS10, HS15 and HS20) with one group kept as control (C). Another three groups were given three doses of the HAs orally at doses of 50, 100 and 200 mg/kg for five consecutive days with one group kept as a control (C). Systolic (SBP) and diastolic (DBP) blood pressures, as well as heart rate (HR), were measured weekly. After the experimental protocols, the left ventricles (LV) of all rats were obtained. Capillary surface area density and length density were determined by unbiased sterological methods on 3 μm LV tissue samples from perfusion-fixed hearts. HS ingestion significantly reduced SBP, DBP and LV mass in a dose-dependent fashion but did not affect the HR. HS significantly increased surface area and length density of myocardial capillaries by 59%, 65% and 86%, and length density by 57%, 77% and 57%, respectively. Myocyte nuclear volume was significantly decreased in HS-treated rats. There was a decrease (although insignificant) in SBP and DBP with HA ingestion compared with controls. These changes suggest that the observed beneficial effect of HS on high BP in SHRs could be mediated through a reduction in the diffusion distance between capillaries and myocytes, as well as new vessel formation. It is proposed that these effects might be beneficial in restoring myocyte normal nutritional status compromised by the hypertrophic state of hypertension.

  7. Osteogenic markers are reduced in bone-marrow mesenchymal cells and femoral bone of young spontaneously hypertensive rats.

    Science.gov (United States)

    Landim de Barros, Thamine; Brito, Victor Gustavo Balera; do Amaral, Caril Constante Ferreira; Chaves-Neto, Antonio Hernandes; Campanelli, Ana Paula; Oliveira, Sandra Helena Penha

    2016-02-01

    Spontaneously hypertensive rats (SHR) and normotensive rats (W) has significant changes in bone metabolism. The purpose of this study was to investigate whether, the genetic predisposition, is sufficient to induce changes in the osteoblast differentiation and osteogenic markers in the BMSCs or in the femoral bone. For this we use young SHR rats without hypertension, but, with genetic predisposition in compared with young W. BMSCs were cultured in a proliferation medium (MEM) or osteogenic medium. Osteogenic differentiation was analyzed by proliferation, total protein, alkaline phosphatase, mineralization, and the mRNA expression of RUNX-2, β-cathenin, osterix, bone morphogenetic protein-2(BMP-2), osteocalcin (OCN), bone sialoprotein (BSP), collagen type I (Col I), and osteopontin (OPN). Osteoblast differentiation in SHR BMSCs (SHRC) had an increased proliferation compared with W BMSCs (WC). After osteogenic induction, there was greater reduction in proliferation in SHR (SHROM) than in W, in the same condition (WOM). On day 7, although no significant difference in the ALP activity was observed between SHROM and WOM, poor mineralization and osteoblast differentiation was noted in SHROM. The Osterix and β-catenin are involved in the reduced osteoblast differentiation in SHROM. The decreased expression of osteoblast-associated proteins such as OCN, BSP, COL I and OPN revealed poor quality of extracellular matrix (ECM) in SHROM. In the femoral bone, the immunostaining of COL1, BALP, OPN and OCN in SHR was decreased compared with the W. TRAP-positive immunoreactions were observed in major extension in the SHR femur. This study is the first to compare osteoblast differentiation in vitro and femoral bone from SHR and W rats. Our results demonstrated that young SHR (4weeks old), without hypertension, but with genetic predisposition, had alterations in osteoblast differentiation of BMSCs and in the femoral bone when compared with their progenitor strain, W. Copyright

  8. Heart and Stroke Foundation of Ontario (HSFO) high blood pressure strategy's hypertension management initiative study protocol.

    Science.gov (United States)

    Tobe, Sheldon W; Moy Lum-Kwong, Margaret; Perkins, Nancy; Von Sychowski, Shirley; Sebaldt, Rolf J; Kiss, Alex

    2008-12-10

    Achieving control of hypertension prevents target organ damage at both the micro and macrovascular level and is a highly cost effective means of lowering the risk for heart attack and stroke particularly in people with diabetes. Clinical trials demonstrate that blood pressure control can be achieved in a large proportion of people. Translating this knowledge into widespread practice is the focus of the Hypertension Management Initiative, which began in 2004 with the goal of improving the management of this chronic health condition by primary care providers and patients in the community. This study will test the effect of a systems change on the management of high blood pressure in real world practice in primary care in Ontario, Canada. The systems change intervention involves an interprofessional educational program bringing together physicians, nurses and pharmacists with tools for both providers and patients to facilitate blood pressure management. Each of two waves of subjects were enrolled over a 6 month period with the initial enrollment between waves separated by 9 months. Blood pressure will be measured with the BpTru automated blood pressure device. To determine the effectiveness of the intervention, a before and after analysis within all subjects will compare blood pressure at baseline to annual measurements for the three year study. To assess whether the intervention has an impact on blood pressure control independent of community trends, a betwen group comparison of baseline blood pressures in the delayed wave will be made with the immediate wave during the same time period, so that the immediate wave has experienced the intervention for at least 9 months. The total enrollment goal is 5,000 subjects. The practice locations include 10 Family Health Teams (FHTs) and 1 Community Health Centre (CHC) and approximately 49 primary care physicians, 15 nurse practitioners, 37 registered nurses and over 150 community pharmacists across the 11 communities

  9. Heart and Stroke Foundation of Ontario (HSFO high blood pressure strategy's hypertension management initiative study protocol

    Directory of Open Access Journals (Sweden)

    Von Sychowski Shirley

    2008-12-01

    Full Text Available Abstract Background Achieving control of hypertension prevents target organ damage at both the micro and macrovascular level and is a highly cost effective means of lowering the risk for heart attack and stroke particularly in people with diabetes. Clinical trials demonstrate that blood pressure control can be achieved in a large proportion of people. Translating this knowledge into widespread practice is the focus of the Hypertension Management Initiative, which began in 2004 with the goal of improving the management of this chronic health condition by primary care providers and patients in the community. Methods This study will test the effect of a systems change on the management of high blood pressure in real world practice in primary care in Ontario, Canada. The systems change intervention involves an interprofessional educational program bringing together physicians, nurses and pharmacists with tools for both providers and patients to facilitate blood pressure management. Each of two waves of subjects were enrolled over a 6 month period with the initial enrollment between waves separated by 9 months. Blood pressure will be measured with the BpTru ® automated blood pressure device. To determine the effectiveness of the intervention, a before and after analysis within all subjects will compare blood pressure at baseline to annual measurements for the three year study. To assess whether the intervention has an impact on blood pressure control independent of community trends, a betwen group comparison of baseline blood pressures in the delayed wave will be made with the immediate wave during the same time period, so that the immediate wave has experienced the intervention for at least 9 months. The total enrollment goal is 5,000 subjects. The practice locations include 10 Family Health Teams (FHTs and 1 Community Health Centre (CHC and approximately 49 primary care physicians, 15 nurse practitioners, 37 registered nurses and over 150

  10. Prediction of hemorrhagic transformation after experimental ischemic stroke using MRI-based algorithms

    NARCIS (Netherlands)

    Bouts, Mark. J. R. J.; Tiebosch, Ivo A.C.W.; Rudrapatna, Umesh S; van der Toorn, Annette; Wu, Ona; Dijkhuizen, Rick M.

    2017-01-01

    Estimation of hemorrhagic transformation (HT) risk is crucial for treatment decision–making after acute ischemic stroke. We aimed to determine the accuracy of multiparametric MRI-based predictive algorithms in calculating probability of HT after stroke. Spontaneously, hypertensive rats were

  11. Improved In Vivo Efficacy of Anti-Hypertensive Biopeptides Encapsulated in Chitosan Nanoparticles Fabricated by Ionotropic Gelation on Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Shehu Muhammad Auwal

    2017-12-01

    Full Text Available Recent biotechnological advances in the food industry have led to the enzymatic production of angiotensin I-converting enzyme (ACE-inhibitory biopeptides with a strong blood pressure lowering effect from different food proteins. However, the safe oral administration of biopeptides is impeded by their enzymatic degradation due to gastrointestinal digestion. Consequently, nanoparticle (NP-based delivery systems are used to overcome these gastrointestinal barriers to maintain the improved bioavailability and efficacy of the encapsulated biopeptides. In the present study, the ACE-inhibitory biopeptides were generated from stone fish (Actinopyga lecanora protein using bromelain and stabilized by their encapsulation in chitosan (chit nanoparticles (NPs. The nanoparticles were characterized for in vitro physicochemical properties and their antihypertensive effect was then evaluated on spontaneously hypertensive rats (SHRs. The results of a physicochemical characterization showed a small particle size of 162.70 nm, a polydispersity index (pdi value of 0.28, a zeta potential of 48.78 mV, a high encapsulation efficiency of 75.36%, a high melting temperature of 146.78 °C and an in vitro sustained release of the biopeptides. The results of the in vivo efficacy indicated a dose-dependent blood pressure lowering effect of the biopeptide-loaded nanoparticles that was significantly higher (p < 0.05 compared with the un-encapsulated biopeptides. Moreover, the results of a morphological examination using transmission electron microscopy (TEM demonstrated the nanoparticles as homogenous and spherical. Thus, the ACE-inhibitory biopeptides stabilized by chitosan nanoparticles can effectively reduce blood pressure for an extended period of time in hypertensive individuals.

  12. The incidence of vasculitis is increased in female stroke-prone ...

    African Journals Online (AJOL)

    Background: Vascular changes in hypertension share common characteristics with inflammatory wall injury. Since it is known that chronic inflammatory diseases are frequently more prevalent in females, this study tested the hypothesis that vasculitis would be more evident in female stroke-prone spontaneously hypertensive ...

  13. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

    Science.gov (United States)

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-10-07

    High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.

  14. Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat

    Czech Academy of Sciences Publication Activity Database

    Liška, F.; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Kazdová, L.; Starker, C.G.; Voytas, D.F.; Izsvák, Z.; Mancini, M.; Šeda, O.; Křen, V.; Pravenec, Michal

    2017-01-01

    Roč. 69, č. 6 (2017), s. 1084-1091 ISSN 0194-911X R&D Projects: GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fibrosis * hypertension * hypertrophy * left ventricular rats * inbred * SHR * transcriptome Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (UMG-J) Impact factor: 6.857, year: 2016

  15. Impact of achieved blood pressure on renal function decline and first stroke in hypertensive patients with chronic kidney disease.

    Science.gov (United States)

    Li, Youbao; Liang, Min; Jiang, Chongfei; Wang, Guobao; Li, Jianping; Zhang, Yan; Fan, Fangfang; Sun, Ningling; Cui, Yiming; He, Mingli; Tang, Genfu; Yin, Delu; Cheng, Xiaoshu; Wang, Binyan; Huo, Yong; Xu, Xin; Hou, Fan Fan; Xu, Xiping; Qin, Xianhui

    2018-03-01

    The effect of achieved blood pressure (BP) on first stroke and renal function decline among hypertensive patients with mild to moderate chronic kidney disease (CKD) is still uncertain. In total, 3230 hypertensive patients with estimated glomerular filtration rate 30-60 mL/min/1.73 m2 and/or proteinuria were included in the present analyses. Eligible participants were randomly assigned to a daily treatment of a combined enalapril 10 mg and folic acid 0.8 mg tablet or an enalapril 10 mg tablet alone. Participants were followed up every 3 months. The study outcomes included first stroke and the progression of CKD. The median antihypertensive treatment duration was 4.7 years. Compared with participants with a time-averaged on-treatment systolic blood pressure (SBP) of 135 to ≤140 mmHg, the incidence of total first stroke [1.7% versus 3.3%; hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in those with a time-averaged SBP of ≤135 mmHg. Furthermore, a time-averaged diastolic blood pressure (DBP) of ≤80 mmHg, compared with a time-averaged DBP level of 80 to ≤90 mmHg, was significantly related to a decreased risk of hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However, compared with participants with a time-averaged SBP of 135 to ≤140 mmHg, a lower but non-significant trend of CKD progression was found in those with a time-averaged SBP of ≤130 mmHg. A BP treatment level of ≤135/80 mmHg, compared with a BP treatment level of 135-140/80-90 mmHg, could lead to a decreased risk of first stroke in hypertensive patients with mild-to-moderate CKD. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

    Energy Technology Data Exchange (ETDEWEB)

    Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

    1986-03-05

    EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A/sub 4/ hydrolase activity, plasma renin activity (PRA), urinary levels of TxB/sub 2/ and 6-keto-PGF/sub 1..cap alpha../ and aortic conversion of (/sup 14/C)-AA to (/sup 14/C)-6-keto-PGF/sub 1..cap alpha../ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P < 0.001) and retarded the development of hypertension in young SHR rats (178 +/- 6 vs. 218 +/- 4 mmHg in controls, p < 0.001). Platelets showed decreased responsiveness to ADP (3 ..mu..M) and glomerular LTA/sub 4/ hydrolase activity was inhibited. PRA and urinary levels of TxB/sub 2/ and 6-keto-PGF/sub 1..cap alpha../ were not changed. Similarly, there was no change in aortic conversion of (/sup 14/C)-AA to (/sup 14/C)-6-keto-PGF/sub 1..cap alpha../ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function.

  17. The reliability and sensitivity of the National Institutes of Health Stroke Scale for spontaneous intracerebral hemorrhage in an uncontrolled setting.

    Directory of Open Access Journals (Sweden)

    Adrian V Specogna

    Full Text Available BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS is commonly used to measure neurologic function and guide treatment after spontaneous intracerebral hemorrhage (ICH in routine stroke clinics. We evaluated its reliability and sensitivity to detect change with consecutive and unique rater combinations in a real-world setting. METHODS: Conservative measures of interrater reliability (unweighted Kappa (κ, Intraclass Correlation Coefficient (ICC1,1 and sensitivity to detect change (Minimal Detectable Difference (MDD were estimated. Sixty-one repeated ratings were completed within 1 week after ICH by physicians and nurses with no investigator intervention. RESULTS: Reliability (consistency of the NIHSS total score was good for both physicians vs. nurses and nurses vs. nurses (ICC=0.78, 95%CI: 0.58-0.89 and ICC=0.75, 95%CI: 0.55-0.87 respectively in this scenario. Reliability (agreement of items 1C and 9 were excellent (κ>=0.61 for both rater comparisons, however, reliability was poor to fair on most remaining items (κ:0.01-0.60, with item 11 being completely unreliable in this scenario (κ=10 points need to be observed for clinicians to be confident that real changes had occurred within 1 week after ICH.

  18. Features of the alpha-cell population organization in pancreas of spontaneously hypertensive rats (SHR

    Directory of Open Access Journals (Sweden)

    T. V. Abramova

    2017-08-01

    Full Text Available Alpha cells of pancreatic islets constitute the second largest population of pancreatic endocrinocytes, and the glucagon synthesized in them plays an important role in the regulation of glucose homeostasis. At the same time, glucagon-suppressive therapy is defined as the strategically main source of success of therapy for patients with type 2 diabetes mellitus. In clinical practice, diabetes is often associated with hypertension in the metabolic syndrome, which causes interest in the pathophysiology of α-endocrinocytes. The aim of the study was to investigate the distribution parameters of α-cells in the pancreatic islets of SHR and to characterize the morphological and functional state of glucagon-synthesizing endocrinocytes Materials and methods. In the histological sections of the pancreas, glucagon was detected by the immunofluorescence method; the area of pancreatic islets, as well as the number of α-cells in them, the concentration of immunoreactive glucagon in these cells, the specific indices of the distribution of islets, α-cells and glucagon per unit area of the gland. The results were processed with a package of statistical programs, to assess the reliability of the differences in the groups, the Student’s t-test and the Wilcoxon W-test were used. Results. In normoglycemic SHR, the number of islets containing glucagon-synthesizing α-cells was 10% more (p <0.05 than in normotensive Wistar rats. In the pancreatic tissue, single α-endocrine cells were found in rats of both lines, not forming separate islets. In giant islets of SHR there were 72% more α-endocrine cells than in Wistar rats, and in large islets this difference was twofold. Accordingly, α-cells of these islets contributed significantly to higher glucagon levels in the pancreas of hypertensive rats: in giant islets, the amount of the hormone was 80%, and in large islets – 3.6 times higher than in normotensive rats. In this paper we discuss the mechanisms that lead

  19. Inhibition of NADPH Oxidase-Dependent Oxidative Stress in the Rostral Ventrolateral Medulla Mediates the Antihypertensive Effects of Acupuncture in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Wang, Xue-Rui; Yang, Jing-Wen; Ji, Cai-Shuo; Zeng, Xiang-Hong; Shi, Guang-Xia; Fisher, Marc; Liu, Cun-Zhi

    2018-02-01

    Oxidative stress in the rostral ventrolateral medulla (RVLM), where the sympathetic nervous control center is located, contributes to neural mechanisms of hypertension. Acupuncture was previously reported to favorably affect high blood pressure. However, little is known about the effect of acupuncture on oxidative stress-modulated mechanisms in hypertension. This study was designed to evaluate the hypothesis that acupuncture exerts an antihypertensive effect via ameliorating oxidative stress and the redox-sensitive pathway in the RVLM of spontaneously hypertensive rats. Two weeks of acupuncture reduced blood pressure and sympathetic nervous system activity in spontaneously hypertensive rats. Oxidative stress in the RVLM was alleviated by acupuncture, accompanied by a decrease in nicotinamide adenine dinucleotide phosphate oxidase activity and expression of its subunits. Acupuncture significantly altered the mitogen-activated protein kinases signaling pathway as assessed by pathway enrichment analysis in a gene chip assay. The phosphorylation of p38 mitogen-activated protein kinases and extracellular signal-regulated protein kinase 1/2, but not Jun N-terminal kinase, was downregulated by acupuncture. Microinjection bilaterally of the superoxide dismutase mimetic tempol, nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin, or diphenyleneiodonium chloride into the RVLM mimicked the antihypertensive effect of acupuncture. In contrast, the nicotinamide adenine dinucleotide phosphate oxidase agonist tetrabromocinnamic acid abolished the beneficial effects of acupuncture. Furthermore, injection of capsaicin or surgical sectioning of the sciatic nerve abolished the antihypertensive effect of acupuncture. We conclude that acupuncture decreases high blood pressure and nicotinamide adenine dinucleotide phosphate oxidase in the RVLM of spontaneously hypertensive rats. The mitogen-activated protein kinases and the sciatic nerve are involved in the mechanism

  20. Heart rate variability and stroke volume variability to detect central hypovolemia during spontaneous breathing and supported ventilation in young, healthy volunteers

    International Nuclear Information System (INIS)

    Elstad, Maja; Walløe, Lars

    2015-01-01

    Cardiovascular oscillations exist in many different variables and may give important diagnostic and prognostic information in patients. Variability in cardiac stroke volume (SVV) is used in clinical practice for diagnosis of hypovolemia, but currently is limited to patients on mechanical ventilation. We investigated if SVV and heart rate variability (HRV) could detect central hypovolemia in spontaneously breathing humans: We also compared cardiovascular variability during spontaneous breathing with supported mechanical ventilation.Ten subjects underwent simulated central hypovolemia by lower body negative pressure (LBNP) with >10% reduction of cardiac stroke volume. The subjects breathed spontaneously and with supported mechanical ventilation. Heart rate, respiratory frequency and mean arterial blood pressure were measured. Stroke volume (SV) was estimated by ModelFlow (Finometer). Respiratory SVV was calculated by: 1) SVV% = (SVmax − SVmin)/SVmean during one respiratory cycle, 2) SVIntegral from the power spectra (Fourier transform) at 0.15–0.4 Hz and 3) SVV-norm = (√SVIntegral)/SVmean. HRV was calculated by the same methods.During spontaneous breathing two measures of SVV and all three measures of HRV were reduced during hypovolemia compared to baseline. During spontaneous breathing SVIntegral and HRV% were best to detect hypovolemia (area under receiver operating curve 0.81). HRV% ≤ 11% and SVIntegral ≤ 12 ml 2 differentiated between hypovolemia and baseline during spontaneous breathing.During supported mechanical ventilation, none of the three measures of SVV changed and two of the HRV measures were reduced during hypovolemia. Neither measures of SVV nor HRV were classified as a good detector of hypovolemia.We conclude that HRV% and SVIntegral detect hypovolemia during spontaneous breathing and both are candidates for further clinical testing. (paper)

  1. Caffeine improves spatial learning deficits in an animal model of attention deficit hyperactivity disorder (ADHD) -- the spontaneously hypertensive rat (SHR).

    Science.gov (United States)

    Prediger, Rui D S; Pamplona, Fabrício A; Fernandes, Daniel; Takahashi, Reinaldo N

    2005-12-01

    The spontaneously hypertensive rat (SHR) is generally considered to be a suitable genetic model for the study of attention deficit hyperactivity disorder (ADHD), since it displays hyperactivity, impulsivity, poorly sustained attention, and deficits in learning and memory processes. Converging evidence suggests a primary role of disturbance in the dopaminergic neurotransmission in ADHD patients and in SHR, and in addition, some studies have also demonstrated alterations in adenosinergic neurotransmission in SHR. In the present study, adult female Wistar (WIS) and SHR rats received caffeine (1-10 mg/kg i.p.) 30 min before training, immediately after training, or 30 min before a test session in the spatial version of the Morris water maze. The effect of caffeine administration on WIS and SHR blood pressure was also measured. SHR needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of WIS rats in the test session (48 h later), demonstrating a selective deficit in spatial learning. Pre-training administration of caffeine (1-10 mg/kg i.p.) improved this spatial learning deficit in SHR, but did not alter the WIS performance. In contrast, post-training administration of caffeine (3 mg/kg i.p.) did not alter the SHR test performance, but increased memory retention in WIS rats. No dose of caffeine tested altered the mean blood pressure of WIS or SHR. These results demonstrate a selective spatial learning deficit in SHR which can be attenuated by pre-training administration of caffeine. In addition, the present findings indicate that the spatial learning deficit in SHR is not directly related to hypertension.

  2. Renal proximal tubular reabsorption is reduced in adult spontaneously hypertensive rats: roles of superoxide and Na+/H+ exchanger 3.

    Science.gov (United States)

    Panico, Carolina; Luo, Zaiming; Damiano, Sara; Artigiano, Francesca; Gill, Pritmohinder; Welch, William J

    2009-12-01

    Proximal tubule reabsorption is regulated by systemic and intrinsic mechanisms, including locally produced autocoids. Superoxide, produced by NADPH oxidase enhances NaCl transport in the loop of Henle and the collecting duct, but its role in the proximal tubule is unclear. We measured proximal tubule fluid reabsorption (Jv) in WKY rats and compared that with Jv in the spontaneously hypertensive rat (SHR), a model of enhanced renal superoxide generation. Rats were treated with the NADPH oxidase inhibitor apocynin (Apo) or with small interfering RNA for p22(phox), which is the critical subunit of NADPH oxidase. Jv was lower in SHR compared with Wistar-Kyoto rats (WKY; WKY: 2.3+/-0.3 vs SHR: 1.1+/-0.2 nL/min per millimeter; n=9 to 11; P<0.001). Apo and small interfering RNA to p22(phox) normalized Jv in SHRs but had no effect in WKY rats. Jv was reduced in proximal tubules perfused with S-1611, a highly selective inhibitor of the Na(+)/H(+) exchanger 3, the major Na(+) uptake pathway in the proximal tubule, in WKY rats but not in SHRs. Pretreatment with Apo restored an effect of S-1611 to reduce Jv in the SHRs (SHR+Apo: 2.9+/-0.4 vs SHR+Apo+S-1611: 1.0+/-0.3 nL/min per millimeter; P<0.001). However, because expression of the Na(+)/H(+) exchanger 3 was similar between SHR and WKY rats, this suggests that superoxide affects Na(+)/H(+) exchanger 3 activity. Direct microperfusion of Tempol or Apo into the proximal tubule also restored Jv in SHRs. In conclusion, superoxide generated by NADPH oxidase inhibits proximal tubule fluid reabsorption in SHRs. This finding implies that proximal tubule fluid reabsorption is regulated by redox balance, which may have profound effects on ion and fluid homeostasis in the hypertensive kidney.

  3. Effects of kimchi supplementation on blood pressure and cardiac hypertrophy with varying sodium content in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Seung-Min; Cho, Yoonsu; Chung, Hye-Kyung; Shin, Dong-Hyuk; Ha, Woel-Kyu; Lee, Sang-Chul; Shin, Min-Jeong

    2012-08-01

    We tested the effects of dietary intake of freeze-dried Korean traditional fermented cabbage (generally known as kimchi) with varying amounts of sodium on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Wistar-Kyoto rats (WKY), as a control group, received a regular AIN-76 diet, and the SHRs were divided into four groups. The SHR group was fed a regular diet without kimchi supplementation, the SHR-L group was fed the regular diet supplemented with low sodium kimchi containing 1.4% salt by wet weight, which was provided in a freeze-dried form, the SHR-M group was supplemented with medium levels of sodium kimchi containing 2.4% salt, and the SHR-H group was supplemented with high sodium kimchi containing 3.0% salt. Blood pressure was measured over 6 weeks, and cardiac hypertrophy was examined by measuring heart and left ventricle weights and cardiac histology. SHRs showed higher blood pressure compared to that in WKY rats, which was further elevated by consuming high sodium containing kimchi but was not influenced by supplementing with low sodium kimchi. None of the SHR groups showed significant differences in cardiac and left ventricular mass or cardiomyocyte size. Levels of serum biochemical parameters, including blood urea nitrogen, creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sodium, and potassium were not different among the groups. Elevations in serum levels of aldosterone in SHR rats decreased in the low sodium kimchi group. These results suggest that consuming low sodium kimchi may not adversely affect blood pressure and cardiac function even under a hypertensive condition.

  4. Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats.

    Science.gov (United States)

    Ahmad, Fiaz Ud Din; Sattar, Munavvar A; Rathore, Hassaan A; Tan, Yong Chia; Akhtar, Safia; Jin, Oh Hui; Pei, Yen Pei; Abdullah, Nor A; Johns, Edward J

    2014-05-01

    Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n=6) were treated for 4 weeks either as controls or received NaHS (SHR+NaHS), tempol (SHR+Tempol), or NaHS plus tempol (SHR+NaHS +Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all ptempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20-22% vs. ∼11-15% and ∼10-14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all ptempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.

  5. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.

    Science.gov (United States)

    Huo, Yong; Li, Jianping; Qin, Xianhui; Huang, Yining; Wang, Xiaobin; Gottesman, Rebecca F; Tang, Genfu; Wang, Binyan; Chen, Dafang; He, Mingli; Fu, Jia; Cai, Yefeng; Shi, Xiuli; Zhang, Yan; Cui, Yimin; Sun, Ningling; Li, Xiaoying; Cheng, Xiaoshu; Wang, Jian'an; Yang, Xinchun; Yang, Tianlun; Xiao, Chuanshi; Zhao, Gang; Dong, Qiang; Zhu, Dingliang; Wang, Xian; Ge, Junbo; Zhao, Lianyou; Hu, Dayi; Liu, Lisheng; Hou, Fan Fan

    2015-04-07

    Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no

  6. Age-related weakening of baroreflex-mediated sympathetic activity in spontaneously hypertensive rats in response to blood pressure reduction.

    Science.gov (United States)

    Prados, P; Santa, T; Fukushima, T; Homma, H; Kasai, C; Martin, M A; del Castillo, B; Imai, K

    1998-09-01

    Nicardipine, a dihydropyridine type calcium channel blocker, was infused into 4-, 6-, and 23-wk-old spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia and ventilation, n = 4) through the left femoral vein, resulting in the reduction of blood pressure. In each rat, mean arterial blood pressure, heart rate, and the concentration of plasma catecholamines (CAs), norepinephrine (NE), and epinephrine (E) were concomitantly determined, and the correlations between these three variables were studied. During the infusion of nicardipine, the plasma concentration of CAs was measured with an automatic detection system in blood samples collected from the right femoral artery of each rat. The reduction in blood pressure induced by nicardipine brought about an increase in plasma CA levels. The blood pressure correlated well with the logarithm of plasma NE or E concentration according to the formula Y= -alpha log (X) + m (Y, blood pressure; X, concentration of plasma NE or E; a, slope; and m, intercept). The slopes (as) of 6-wk-old and 23-wk-old SH rats were significantly greater than those of aged-matched WKY rats, meaning that the increment in plasma CAs in response to a decrease in blood pressure was smaller in SH than in WKY rats of similar ages. However, no significant differences were found between the as of 4-wk-old SH and WKY rats. We conclude that the increment in the baroreflex-mediated sympathetic activity in response to a drop in blood pressure induced by nicardipine is similar or greater in prehypertensive SH than in normotensive WKY 4-wk-old rats, while the increment becomes smaller in SH rats with the onset of hypertension (6-wk-old rats), and is much less in fully hypertensive adult (23-wk-old) SH rats than in age-matched WKY rats. On the basis of these findings and previous data obtained by neurography, we conclude that plasma CAs can be used to evaluate baroreflex-mediated sympathetic

  7. Receptor cleavage and P-selectin-dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat

    Science.gov (United States)

    Chen, Angela Y.; Ha, Jessica N.; DeLano, Frank A.; Schmid-Schönbein, Geert W.

    2012-01-01

    The SHR, a genetic model for hypertension and the metabolic syndrome, has attenuated leukocyte adhesion to the postcapillary endothelium by an unknown mechanism. Based on recent evidence of elevated levels of MMPs in plasma and on microvascular endothelium of the SHR with cleavage of several receptor types, we hypothesize that the reduced leukocyte-endothelial interaction is a result of enhanced proteolytic cleavage of P-selectin on the postcapillary endothelium and PSGL-1 on leukocytes. The attenuated rolling interactions of SHR leukocytes with the endothelium were restored by chronic treatment with a broad-spectrum MMP inhibitor (CGS) for 24 weeks. The SHR MMP levels, in plasma and mesentery, as well as the systolic blood pressure, decreased significantly with treatment. In the SHR mesentery, labeling of P-selectin in the postcapillary venules by immunohistochemistry demonstrated, on average, a 31% lower extracellular P-selectin density compared with the normotensive WKY. A significantly lower extracellular PSGL-1 density on the membranes of SHR neutrophils compared with the WKY also supported our hypothesis. In vivo stimulation of the mesenteric postcapillary venules with histamine demonstrated that the SHR had an attenuated response, as measured by leukocyte rolling velocity on the endothelium. The reduced P-selectin and PSGL-1 density, on SHR postcapillary endothelium and on SHR leukocytes, respectively, was restored significantly by chronic MMP inhibition. The impaired ability of SHR leukocytes to reduce rolling velocity upon inflammatory stimulation led to fewer firmly adhered leukocytes to the endothelium as a contributor to immune suppression. PMID:22566571

  8. Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

    International Nuclear Information System (INIS)

    Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

    1986-01-01

    EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A 4 hydrolase activity, plasma renin activity (PRA), urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ and aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P 4 hydrolase activity was inhibited. PRA and urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ were not changed. Similarly, there was no change in aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function

  9. Effects of PPARγ Agonist Pioglitazone on Redox-Sensitive Cellular Signaling in Young Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Ima Dovinová

    2013-01-01

    Full Text Available PPARγ receptor plays an important role in oxidative stress response. Its agonists can influence vascular contractility in experimental hypertension. Our study was focused on the effects of a PPARγ agonist pioglitazone (PIO on blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling at the central (brainstem, BS and peripheral (left ventricle, LV levels in young prehypertensive rats. 5-week-old SHR were treated either with PIO (10 mg/kg/day, 2 weeks or with saline using gastric gavage. Administration of PIO significantly slowed down blood pressure increase and improved lipid profile and aortic relaxation after insulin stimulation. A significant increase in PPARγ expression was found only in BS, not in LV. PIO treatment did not influence NOS changes, but had tissue-dependent effect on SOD regulation and increased SOD activity, observed in LV. The treatment with PIO differentially affected also the levels of other intracellular signaling components: Akt kinase increased in the the BS, while β-catenin level was down-regulated in the BS and up-regulated in the LV. We found that the lowering of blood pressure in young SHR can be connected with insulin sensitivity of vessels and that β-catenin and SOD levels are important agents mediating PIO effects in the BS and LV.

  10. Hypertension

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for hypertension hyperlipidemia. The data is provided by three managed care organizations in Allegheny County...

  11. Rhodiola-water extract induces β-endorphin secretion to lower blood pressure in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Wei-Jing; Chung, Hsien-Hui; Cheng, Yung-Ze; Lin, Hung Jung; Cheng, Juei-Tang

    2013-10-01

    Rhodiola rosea (Rhodiola) is grown at high altitudes and northern latitudes. It is mainly used clinically as an adaptogen, but antihypertensive effects have been reported for the extract. These have not been well investigated, so in the present study, we evaluated the effect of Rhodiola-water extract on blood pressure in spontaneously hypertensive rats (SHRs) and investigated the potential mechanism(s) for this action. In conscious male SHRs, systolic blood pressure (SBP) and heart rate were recorded using the tail-cuff method. Plasma β-endorphin was measured by enzyme-linked immunosorbent assay. Rhodiola-water extract decreased SBP in SHRs in a dose-dependent manner, and this action was more significant than that in normal group named Wistar-Kyoto (WKY) rats. This reduction of SBP in SHRs was inhibited by pretreatment with the selective opioid μ-receptor antagonist, cyprodime, but not by naloxonazine, an antagonist specific to opioid μ1-receptor. Also, the SBP-lowering action of Rhodiola-water extract was attenuated in adrenalectomized SHRs. Moreover, Rhodiola-water extract dose-dependently increased β-endorphin release in SHRs, and the elevation of β-endorphin in SHRs was higher than that in WKY. Thus, we suggest that Rhodiola-water extract can induce release of β-endorphin to lower SBP in SHRs. Copyright © 2012 John Wiley & Sons, Ltd.

  12. The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Matsuu, Mutsumi; Shichijo; Kazuko; Nakamura, Yasuko; Ikeda, Yuji; Naito, Shinji; Ito, Masahiro; Okaichi, Kumio; Sekine, Ichiro

    2000-01-01

    To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells. (author)

  13. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1991-01-01

    The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

  15. Effect of arotinolol on hemodynamics and plasma atrial natriuretic peptide at rest and during stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Yamamoto, J; Matsubara, H; Nakai, M

    1989-01-01

    We investigated the effects of chronic treatment with arotinolol, a beta-blocker with weak alpha-blocking potency, on hemodynamics and plasma levels of catecholamines and atrial natriuretic peptide (ANP) at rest and during stress in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. At rest, arotinolol treatment decreased mean arterial pressure (MAP), cardiac index (CI) and heart rate (HR), with no changes in total peripheral resistance index or regional hemodynamics in SHR. Acute stress caused more remarkable hemodynamic changes in SHR. During stress, arotinolol decreased MAP, CI and HR, and reduced myocardial and skeletal muscle flow and splanchnic, renal, cerebral and cutaneous vascular resistance in SHR. Arotinolol's effects were much less in WKY. Stress also increased the plasma catecholamine and ANP levels in SHR. Arotinolol raised these hormones in both strains at rest and in SHR during stress. Thus, arotinolol treatment exerted greater suppressive effects on the resting and stressed hemodynamics in SHR, with associated increases in the plasma catecholamine and ANP levels.

  16. Augmentation of ferulic acid-induced vasorelaxation with aging and its structure importance in thoracic aorta of spontaneously hypertensive rats.

    Science.gov (United States)

    Fukuda, Toshihiko; Kuroda, Takahiro; Kono, Miki; Hyoguchi, Mai; Tanaka, Mitsuru; Matsui, Toshiro

    2015-10-01

    Aging deteriorates vascular functions such as vascular reactivity and stiffness. Thus far, various reports suggest that bioactive compounds can improve vascular functions. However, few age-related studies of natural bioactive compounds are available. The present study attempted to evaluate age-related vasorelaxation of bioactive cinnamic acids, caffeic acid, and ferulic acid using aged rat thoracic aorta. Vasorelaxation was evaluated in thoracic aorta from both 8, 18, and 40 weeks old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) respectively. The result indicated that caffeic acid possessed the vasorelaxation regardless of aging in WKY and SHR. Moreover, the vasorelaxation of ferulic acid enhanced with aging in SHR. The vasorelaxation behavior was acted in an endothelium-independent manner. To access structure importance of enhanced vasorelaxation, analogues of ferulic acid were tested. In 40 weeks old SHR, 3,4-dimethoxycinnamic acid and coniferyl alcohol exhibited equivalent vasorelaxation activity with ferulic acid, providing the structural importance of methoxy-modified 3-position on the phenyl ring and 2-propenoic moiety. These results firstly demonstrated that enhanced vasorelaxation of ferulic acid with aging and 3,4-dimethoxycinnamic acid and coniferyl alcohol, along with ferulic acid, might exhibit the therapeutic potential of vasoactive power with aging.

  17. Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

    Directory of Open Access Journals (Sweden)

    Ryu Jong

    2010-12-01

    Full Text Available Abstract Substrains of the Spontaneously Hypertensive rat (SHR, a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD, have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD. However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA test, and its response on the conditioned place preference (CPP paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj. Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine.

  18. Pharmacokinetic-pharmacodynamic modeling of the antihypertensive interaction between azilsartan medoxomil and chlorthalidone in spontaneously hypertensive rats.

    Science.gov (United States)

    Kumar Puttrevu, Santosh; Ramakrishna, Rachumallu; Bhateria, Manisha; Jain, Moon; Hanif, Kashif; Bhatta, Rabi Sankar

    2017-05-01

    A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

  19. Defective fatty acid uptake in the spontaneously hypertensive rat is a primary determinant of altered glucose metabolism, hyperinsulinemia, and myocardial hypertrophy

    Czech Academy of Sciences Publication Activity Database

    Hajri, T.; Ibrahimi, A.; Coburn, C. T.; Knapp jr., F. F.; Kurtz, T.; Pravenec, Michal; Abumrad, N. A.

    2001-01-01

    Roč. 276, č. 26 (2001), s. 23661-23666 ISSN 0021-9258 Grant - others:NIH-OER(US) RO1-DK33301; AHA(US) AHA0020639T; AHA(US) AHA0030345T Institutional research plan: CEZ:AV0Z5011922 Keywords : fatty acid transperter * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.258, year: 2001

  20. Fumaric Acid Esters Can Block Pro-Inflammatory Actions of Human CRP and Ameliorate Metabolic Disturbances in Transgenic Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Mlejnek, Petr; Landa, Vladimír; Šimáková, Miroslava; Strnad, Hynek; Oliyarnyk, O.; Škop, V.; Kazdová, L.; Kurtz, T.; Pravenec, Michal

    2014-01-01

    Roč. 9, č. 7 (2014), e101906 E-ISSN 1932-6203 R&D Projects: GA MZd(CZ) NT14325; GA MŠk(CZ) LH12061; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fumaric acid esters * C-reactive protein * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  1. Short-term blood pressure variability in acute stroke: post hoc analysis of the controlling hypertension and hypotension immediately post stroke and continue or stop post-stroke antihypertensives collaborative study trials.

    Science.gov (United States)

    Manning, Lisa S; Mistri, Amit K; Potter, John; Rothwell, Peter M; Robinson, Thompson G

    2015-06-01

    Short-term blood pressure variability (BPV) may predict outcome in acute stroke. We undertook a post hoc analysis of data from 2 randomized controlled trials to determine the effect of short-term BPV on 2-week outcome. Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) was a trial of BP-lowering, enrolling 179 acute stroke patients (onset3) at 2 weeks. Seven hundred six (92.5%) and 171 (95.5%) participants were included in the analysis for the COSSACS and CHHIPS data sets, respectively. Adjusted logistic regression analyses revealed no statistically significant associations between any of the included BPV parameters with 2-week death or disability in either study data set: COSSACS, odds ratio SD systolic BP 0.98 (0.78-1.23); CHHIPS, odds ratio SD systolic BP 0.97 (0.90-1.11). When derived from casual cuff BP measures, short-term BPV is not a useful predictor of early (2 weeks) outcome after acute stroke. Differing methodology may account for the discordance with previous studies indicating long-term (casual BPV) and short-term (beat-to-beat BPV) prognostic value. COSSACS was registered on the International Standard Randomised Controlled Trial Register; URL: http://www.isrctn.com. Unique identifier: ISRCTN89712435. CHHIPS was registered on the National Research Register; URL: http://public.ukcrn.org.uk. Unique identifier: N0484128008. © 2015 American Heart Association, Inc.

  2. Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients: A Population-Based, Prospective Cohort Study.

    Science.gov (United States)

    Han, Liyuan; Wu, Qunhong; Wang, Changyi; Hao, Yanhua; Zhao, Jinshun; Zhang, Lina; Fan, Rui; Liu, Yanfen; Li, Runhua; Chen, Zhongwei; Zhang, Tao; Chen, Sihan; Ma, Jianping; Liu, Shengyuan; Peng, Xiaolin; Duan, Shiwei

    2015-07-01

    Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries. A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation. After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65-2.89), 2.40 (1.56-3.67), and 2.73 (1.83-4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 μmol/L (27.92%) in patients with essential hypertension. Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels. © 2015 American Heart Association, Inc.

  3. Aortic and carotid arterial stiffness and epigenetic regulator gene expression changes precede blood pressure rise in stroke-prone Dahl salt-sensitive hypertensive rats.

    Science.gov (United States)

    Herrera, Victoria L; Decano, Julius L; Giordano, Nicholas; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2014-01-01

    Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.

  4. Aortic and carotid arterial stiffness and epigenetic regulator gene expression changes precede blood pressure rise in stroke-prone Dahl salt-sensitive hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV, precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain, blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.

  5. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    Directory of Open Access Journals (Sweden)

    Giuseppina Mattace Raso

    Full Text Available Palmitoylethanolamide (PEA, a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR. Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF, and renin angiotensin system (RAS modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the

  6. β- and α2-Adrenoceptor Control of Vascular Tension and Catecholamine Release in Female Normotensive and Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Berg, Torill

    2017-01-01

    As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower blood pressure than male SHR. In male, normotensive rats (WKY), α 2 - and β 1+2 -adrenoceptors (AR) reciprocally controlled catecholamine release and vascular smooth muscle tension. This interaction was malfunctioning in male SHR. The present study analyzed if a favorable shift in the α 2 /β 1+2 AR interaction may represent an antihypertensive protection in females. Female SHR (early hypertension, 12-14 weeks) and age-matched WKY were infused with tyramine (15 min) to stimulate norepinephrine (NE) release through the reuptake transporter, consequently preventing reuptake. Presynaptic control of vesicular release was therefore reflected as differences in overflow to plasma. The released NE increased total peripheral vascular resistance (TPR). The results showed that β 1>2 AR facilitated tyramine-stimulated NE release in both strains, also in the presence of α 2 AR-antagonist (L-659,066). βAR-antagonist (atenolol-β 1 , ICI-118551-β 2 , nadolol-β 1+2 ) had no effect on the increased secretion of epinephrine after L-659,066 in WKY, but β 1>2 AR-antagonist augmented the L-659,066-induced increase in the secretion of epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater effect in WKY than SHR, whereas β 1or2 -selective antagonists did not. One βAR-subtype may therefore substitute for the other. When both β 1+2 AR were blocked, α 2 AR-antagonist still reduced the TPR response in WKY but not SHR. Thus, α 2 /β 1+2 AR reciprocally controlled catecholamine release, with a particular negative β 1 AR-influence on α 2 AR-auto-inhibition of epinephrine secretion in SHR. Moreover, in these female rats, β 1/2 AR-independent α 2 AR-mediated vasoconstriction was seen in WKY but not SHR, but β 1/2 AR-mediated vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also in SHR.

  7. Overexpression of AT2R in the solitary-vagal complex improves baroreflex in the spontaneously hypertensive rat.

    Science.gov (United States)

    Ruchaya, Prashant J; Speretta, Guilherme F; Blanch, Graziela Torres; Li, Hongwei; Sumners, Colin; Menani, José V; Colombari, Eduardo; Colombari, Débora S A

    2016-12-01

    The aim of this study was to investigate the physiological effects of increased angiotensin II type 2 receptor (AT2R) expression in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus; NTS/DVM) on baroreflex function in non-anaesthetised normotensive (NT) and spontaneously hypertensive rats (SHR). Ten week old NT Holtzman and SHR were microinjected with either an adeno-associated virus expressing AT2R (AAV2-CBA-AT2R) or enhanced green fluorescent protein (control; AAV2-CBA-eGFP) into the NTS/DVM. Baroreflex and telemetry recordings were performed on four experimental groups: 1) NTeGFP, 2) NTAT2R, 3) SHReGFP and 4) SHRAT2R (n=4-7/group). Following in-vivo experimental procedures, brains were harvested for gene expression analysis. Impaired bradycardia in SHReGFP was restored in SHR rats overexpressing AT2R in the NTS/DMV. mRNA levels of angiotensin converting enzyme decreased and angiotensin converting enzyme 2 increased in the NTS/DMV of SHRAT2R compared to SHReGFP. Increased levels of pro-inflammatory cytokine mRNA levels in the SHReGFP group also decreased in the SHRAT2R group. AT2R overexpression did not elicit any significant change in mean arterial pressure (MAP) in all groups from baseline to 4weeks post viral transfection. Both SHReGFP and SHRAT2R showed a significant elevation in MAP compared to the NTeGFP and NTAT2R groups. Increased AT2R expression within the NTS/DMV of SHR was effective at improving baroreflex function but not MAP. We propose possible mediators involved in improving baroreflex are in the ANG II/ACE2 axis, suggesting a potential beneficial modulatory effect of AT2R overexpression in the NTS/DMV of neurogenic hypertensive rats. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Improvement of spontaneous language in stroke patients with chronic aphasia treated with music therapy: a randomized controlled trial.

    Science.gov (United States)

    Raglio, Alfredo; Oasi, Osmano; Gianotti, Marta; Rossi, Agnese; Goulene, Karine; Stramba-Badiale, Marco

    2016-01-01

    The aim of this research is to evaluate the effects of active music therapy (MT) based on free-improvisation (relational approach) in addition to speech language therapy (SLT) compared with SLT alone (communicative-pragmatic approach: Promoting Aphasic's Communicative Effectiveness) in stroke patients with chronic aphasia. The experimental group (n = 10) was randomized to 30 MT individual sessions over 15 weeks in addition to 30 SLT individual sessions while the control group (n = 10) was randomized to only 30 SLT sessions during the same period. Psychological and speech language assessment were made before (T0) and after (T1) the treatments. The study shows a significant improvement in spontaneous speech in the experimental group (Aachener Aphasie subtest: p = 0.020; Cohen's d = 0.35); the 50% of the experimental group showed also an improvement in vitality scores of Short Form Health Survey (chi-square test = 4.114; p = 0.043). The current trial highlights the possibility that the combined use of MT and SLT can lead to a better result in the rehabilitation of patients with aphasia than SLT alone.

  9. Altered heart rate variability in spontaneously hypertensive rats is associated with specific particulate matter components in Detroit, Michigan.

    Science.gov (United States)

    Rohr, Annette C; Kamal, Ali; Morishita, Masako; Mukherjee, Bhramar; Keeler, Gerald J; Harkema, Jack R; Wagner, James G

    2011-04-01

    Exposure to fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] is linked to adverse cardiopulmonary health effects; however, the responsible constituents are not well defined. We used a rat model to investigate linkages between cardiac effects of concentrated ambient particle (CAP) constituents and source factors using a unique, highly time-resolved data set. Spontaneously hypertensive rats inhaled Detroit Michigan, CAPs during summer or winter (2005-2006) for 13 consecutive days. Electrocardiogram data were recorded continuously, and heart rate (HR) and heart rate variability (HRV) metrics were derived. Extensive CAP characterization, including use of a Semicontinuous Elements in Aerosol Sampler (SEAS), was performed, and positive matrix factorization was applied to investigate source factors. Mean CAP exposure concentrations were 518 μg/m(3) and 357 μg/m(3) in the summer and winter, respectively. Significant reductions in the standard deviation of the normal-to-normal intervals (SDNN) in the summer were strongly associated with cement/lime, iron/steel, and gasoline/diesel factors, whereas associations with the sludge factor and components were less consistent. In winter, increases in HR were associated with a refinery factor and its components. CAP-associated HR decreases in winter were linked to sludge incineration, cement/lime, and coal/secondary sulfate factors and most of their associated components. Specific relationships for increased root mean square of the standard deviation of successive normal-to-normal intervals (RMSSD) in winter were difficult to determine because of lack of consistency between factors and associated constituents. Our results indicate that specific modulation of cardiac function in Detroit was most strongly linked to local industrial sources. Findings also highlight the need to consider both factor analytical results and component-specific results when interpreting findings.

  10. Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

    International Nuclear Information System (INIS)

    Cauvin, C.; Hwang, O.; Yamamoto, M.; van Breemen, C.

    1987-01-01

    Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels

  11. Impulsivity in spontaneously hypertensive rats: Within-subjects comparison of sensitivity to delay and to amount of reinforcement.

    Science.gov (United States)

    Orduña, Vladimir; Mercado, Eduardo

    2017-06-15

    Previous research has shown that spontaneously hypertensive rats (SHR) display higher levels of impulsive choice behavior, which is accompanied by a higher sensitivity to the delay of reinforcement, and by a normal sensitivity to the amount of reinforcement. Because those results were based on three different samples of subjects, in the present report we evaluated these three processes in the same individuals. SHR and WIS rats were exposed to concurrent-chains schedules in which the terminal links were manipulated to assess impulsivity, sensitivity to delay, and sensitivity to amount. For exploring impulsivity, a terminal link was associated with a small reinforcer (1 pellet) delivered after a short delay (2s) while the other terminal link was associated with a larger reinforcer (4 pellets) delivered after a longer delay (28s). For assessing sensitivity to delay, both alternatives delivered the same amount of reinforcement (1 pellet) and the only difference between them was in the delay before reinforcement delivery (2s vs 28s). For assessing sensitivity to amount, both alternatives were associated with the same delay (15s), but the alternatives differed in the amount of reinforcement (1 vs 4 pellets). In addition to replicating previously observed effects within-subjects, we were interested in analyzing different aspects of the regularity of rats' actions in the choice task. The results confirmed that previous findings were not a consequence of between-group differences: SHR were more impulsive and more sensitive to delay, while their sensitivity to amount was normal. Analyses of response regularity indicated that SHR subjects were more periodic in their responses to levers and in their feeder entries, had a higher number of short-duration bouts of responding, and made a substantially higher number of switches between the alternatives. We discuss the potential implications of these findings for the possible behavioral mechanisms driving the increased sensitivity

  12. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Hayato Yanagihara

    2016-07-01

    Full Text Available Although telmisartan, an angiotensin II receptor blocker (ARB, has an agonistic action for proliferator-activated receptor (PPAR-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats. To address the issue, telmisartan (2 mg/kg and olmesartan (2 mg/kg, another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR fed a high fat diet (HFD. HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions.

  13. Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

    Science.gov (United States)

    Katakawa, Mayumi; Fukuda, Noboru; Tsunemi, Akiko; Mori, Mari; Maruyama, Takashi; Matsumoto, Taro; Abe, Masanori; Yamori, Yukio

    2016-12-01

    Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

  14. Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

    Directory of Open Access Journals (Sweden)

    S.L. Amaral

    2008-05-01

    Full Text Available Exercise-induced vessel changes modulate arterial pressure (AP in male spontaneously hypertensive rats (SHR. Vascular endothelial growth factor (VEGF is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY rats, 8-9 weeks (200-250 g. Rats were allocated to daily training or remained sedentary for 3 days (N = 23 or 13 weeks (N = 23. After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis and non-locomotor skeletal muscles (temporalis were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days and (SHR = 141%, WKY = 122%, 13 weeks. SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36% simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%. In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%, without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

  15. Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats.

    Science.gov (United States)

    Lopes, P R; Moreira, M C S; Marques, S M; Pinto, I S J; Macedo, L M; Silva, C C; Freiria-Oliveira, A H; Rebelo, A C S; Reis, A A S; Rosa, D A; Ferreira-Neto, M L; Castro, C H; Pedrino, G R

    2016-08-01

    The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280-350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50-60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

  16. Acanthopanax divaricatus var. chiisanensis reduces blood pressure via the endothelial nitric oxide synthase pathway in the spontaneously hypertensive rat model.

    Science.gov (United States)

    Park, Soo-Yeon; Do, Gyeong-Min; Lee, Sena; Lim, Yeni; Shin, Jae-Ho; Kwon, Oran

    2014-09-01

    In this study, we investigated the antihypertensive effects of Acanthopanax divaricatus var. chiisanensis extract (AE) and its active compound, acanthoside D (AD), on arterial blood pressure (BP) in vivo and endothelial function in vitro. We hypothesized that AE has antihypertensive effects, which is attributed to enhancement of endothelial function via the improvement of nitric oxide synthesis or the angiotensin II (Ang II) response. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly divided into 7 groups and then fed the following diets for 14 weeks: WKY fed a normal diet (WN); SHR fed a normal diet (SN); SHR fed a high-cholesterol (HC) diet (SH); SHR fed a HC diet with AE of 150, 300, 600 mg/kg body weight (SH-L, SH-M, SH-H); and SHR fed an HC diet with AD of 600 μg/kg body weight (SH-D). Blood pressure was significantly reduced in the SH-H compared with the SH from week 10 until week 14; BP was also significantly decreased in the SHR fed a HC diet with AE of 300 at week 14. Aortic wall thickness showed a tendency to decrease by AE and AD treatment. The SH-H showed increased endothelial nitric oxide synthase (eNOS) expression in the intima and media, compared with the SH. Furthermore, a significant increase in intracellular nitric oxide production was induced by AE and AD treatment in human umbilical vein endothelial cells. A significant increase of phospho-eNOS was found with a high dose of AE in human umbilical vein endothelial cells but not with AD. These results suggest that AE can regulate BP and improve endothelial function via eNOS-dependent vasodilation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Stroke

    Science.gov (United States)

    ... adjust your treatment as needed. Rehabilitation After a stroke, you may need rehabilitation (rehab) to help you recover. Rehab may include working with speech, physical, and occupational therapists. Language, ... may have trouble communicating after a stroke. You may not be able to find the ...

  18. The CHADS2 Score to Predict Stroke Risk in the Absence of Atrial Fibrillation in Hypertensive Patients Aged 65 Years or Older.

    Science.gov (United States)

    Morillas, Pedro; Pallarés, Vicente; Fácila, Lorenzo; Llisterri, Jose Luis; Sebastián, María Eugenia; Gómez, Manuel; Castilla, Elena; Camarasa, Raquel; Sandin, Miriam; García-Honrubia, Antonio

    2015-06-01

    The CHADS2 score is a proven, essential tool for estimating cardioembolic risk (mainly stroke) in patients with nonvalvular atrial fibrillation, with the purpose of determining the indication for anticoagulant therapy. In this study we analyzed the use of CHADS2 in hypertensive patients without known atrial fibrillation in a Mediterranean population. The study included 887 hypertensive patients aged 65 years or older without atrial fibrillation or anticoagulant therapy, who attended a medical consultation. Data on the patients' main risk factors, cardiovascular history, and medication were collected, basic laboratory analyses and electrocardiography were performed, and the CHADS2 score (heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and previous stroke or transient ischemic attack) was calculated. A clinical follow-up was carried out, recording hospital admissions for a stroke or transient ischemic attack. The median duration of follow-up was 804 days. Mean age was 72.5 (SD,5.7) years, 46.6% were men, 27.8% had diabetes, and 8.6% were smokers. During follow-up, 40 patients were hospitalized for a stroke or transient ischemic attack (4.5%). The event-free survival analysis showed significant differences according to the CHADS2 score (log rank test, P < .001). On multivariate analysis, smoking and CHADS2 ≥3 were independent predictors of stroke or transient ischemic attack. The CHADS2 may be useful for estimating the risk of stroke or transient ischemic attack in hypertensive patients without known atrial fibrillation. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Common variants of ROCKs and the risk of hypertension, and stroke: Two case-control studies and a follow-up study in Chinese Han population.

    Science.gov (United States)

    Yang, Song; Zhao, Yanping; Tian, Yuanrui; Chen, Yanchun; Zhao, Xianghai; Li, Ying; Zhao, Hailong; Chen, Xiaotian; Zhu, Lijun; Fang, Zhengmei; Yao, YingShui; Hu, Zhibing; Shen, Chong

    2018-03-01

    The Rho kinases (ROCKs) are recognized as a critical regulator of vascular functions in cardiovascular disorders. It is crucial to illustrate the association of ROCKs genetic variation and hypertension and/or stroke events. Herein we aimed at investigating the association of ROCK1 and ROCK2 with hypertension and stroke in Chinese Han population. Seven tagSNPs at ROCK1 and ROCK2 were genotyped in a community-based case-control study consisting of 2012 hypertension cases and 2210 normotensive controls and 4128 subjects were further followed up. In stroke case-control study, 1471 ischemic stroke (IS) inpatients and 607 hemorrhagic stroke (HS) inpatients were collected, and 2443 age-matched controls were selected from the follow-up population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by logistic and Cox regression. The community-based case-control study didn't identify any significant tagSNPs associated with hypertension even after adjustment for covariates. The follow-up analysis showed that rs1481280 of ROCK1 significantly associated with incident hypertension (HR=1.130, P=0.048) after adjusting for covariates. rs7589629 and rs978906 of ROCK2 were significantly associated with incident IS (HR=1.373, P=0.004; HR=1.284, P=0.026) respectively. In stroke case-control study, rs288980, rs1481280 and rs7237677 were significantly associated with IS and the adjusted ORs (P values) of additive model were 0.879 (0.010), 0.895 (0.036) and 0.857 (0.002) respectively. Furthermore, rs288980, rs7237677 and rs978906 were significantly associated with HS and the adjusted ORs (P values) of additive model were 0.857 (0.025), 0.848 (0.018) and 0.856 (0.027) respectively. Our findings suggest that ROCK1 and ROCK2 contribute to the genetic susceptibility of hypertension and stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial.

    Science.gov (United States)

    Potter, John F; Robinson, Thompson G; Ford, Gary A; Mistri, Amit; James, Martin; Chernova, Julia; Jagger, Carol

    2009-01-01

    Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke. Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008. 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05). Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute

  1. The effects of pay for performance on disparities in stroke, hypertension, and coronary heart disease management: interrupted time series study.

    Directory of Open Access Journals (Sweden)

    John Tayu Lee

    Full Text Available The Quality and Outcomes Framework (QOF, a major pay-for-performance programme, was introduced into United Kingdom primary care in April 2004. The impact of this programme on disparities in health care remains unclear. This study examines the following questions: has this pay for performance programme improved the quality of care for coronary heart disease, stroke and hypertension in white, black and south Asian patients? Has this programme reduced disparities in the quality of care between these ethnic groups? Did general practices with different baseline performance respond differently to this programme?Retrospective cohort study of patients registered with family practices in Wandsworth, London during 2007. Segmented regression analysis of interrupted time series was used to take into account the previous time trend. Primary outcome measures were mean systolic and diastolic blood pressure, and cholesterol levels. Our findings suggest that the implementation of QOF resulted in significant short term improvements in blood pressure control. The magnitude of benefit varied between ethnic groups with a statistically significant short term reduction in systolic BP in white and black but not in south Asian patients with hypertension. Disparities in risk factor control were attenuated only on few measures and largely remained intact at the end of the study period.Pay for performance programmes such as the QOF in the UK should set challenging but achievable targets. Specific targets aimed at reducing ethnic disparities in health care may also be needed.

  2. The effects of pay for performance on disparities in stroke, hypertension, and coronary heart disease management: interrupted time series study.

    Science.gov (United States)

    Lee, John Tayu; Netuveli, Gopalakrishnan; Majeed, Azeem; Millett, Christopher

    2011-01-01

    The Quality and Outcomes Framework (QOF), a major pay-for-performance programme, was introduced into United Kingdom primary care in April 2004. The impact of this programme on disparities in health care remains unclear. This study examines the following questions: has this pay for performance programme improved the quality of care for coronary heart disease, stroke and hypertension in white, black and south Asian patients? Has this programme reduced disparities in the quality of care between these ethnic groups? Did general practices with different baseline performance respond differently to this programme? Retrospective cohort study of patients registered with family practices in Wandsworth, London during 2007. Segmented regression analysis of interrupted time series was used to take into account the previous time trend. Primary outcome measures were mean systolic and diastolic blood pressure, and cholesterol levels. Our findings suggest that the implementation of QOF resulted in significant short term improvements in blood pressure control. The magnitude of benefit varied between ethnic groups with a statistically significant short term reduction in systolic BP in white and black but not in south Asian patients with hypertension. Disparities in risk factor control were attenuated only on few measures and largely remained intact at the end of the study period. Pay for performance programmes such as the QOF in the UK should set challenging but achievable targets. Specific targets aimed at reducing ethnic disparities in health care may also be needed.

  3. Role of hindbrain melanocortin-4 receptor activity in controlling cardiovascular and metabolic functions in spontaneously hypertensive rats.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Hall, John E

    2015-06-01

    Although we previously demonstrated that activation of central nervous system (CNS) melanocortin3/4 receptors (MC3/4R) play a key role in blood pressure (BP) regulation, especially in spontaneously hypertensive rats (SHRs), the importance of hindbrain MC4R is still unclear. In the present study, we examined the cardiovascular and metabolic effects of chronic inhibition of MC3/4R in the hindbrain of SHRs and normotensive Wistar-Kyoto (WKY) rats. Male WKY rats (n = 6) and SHRs (n = 7) were implanted with telemetry probes to measure BP and heart rate (HR) 24 h/day, and an intracerebroventricular cannula was placed into the fourth ventricle. After 10 days of recovery and 5 days of control measurements, the MC3/4R antagonist (SHU-9119) was infused into the fourth ventricle (1 nmol/h) to antagonize hindbrain MC4R for 10 days, followed by a 5-day recovery period. Chronic hindbrain MC3/4R antagonism significantly increased food intake and body weight in WKY rats (17 ± 1 to 35 ± 2 g/day and 280 ± 8 to 353 ± 8 g) and SHRs (19 ± 2 to 35 ± 2 g/day and 323 ± 7 to 371 ± 11 g), and markedly increased fasting insulin and leptin levels while causing no changes in blood glucose levels (99 ± 4 to 87 ± 4 and 89 ± 5 to 89 ± 4 mg/dl, respectively, for WKY rats and SHRs). Chronic SHU-9119 infusion reduced mean arterial pressure and HR similarly in WKY rats (-8 ± 1 mmHg and -47 ± 3 b.p.m.) and SHRs (-11 ± 3 mmHg and -44 ± 3 b.p.m.). These results suggest that although hindbrain MC4R activity contributes to appetite and HR regulation, it does not play a major role in mediating the elevated BP in SHRs.

  4. Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

    Science.gov (United States)

    Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

    2017-01-01

    Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment

  5. Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Bader Michael

    2008-12-01

    Full Text Available Abstract Background Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs following inhalation of UfCPs (24 h, 172 μg·m-3, to assess whether compromised animals (SHR exhibit a different response pattern compared to the previously studied healthy rats (WKY. Methods Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1, blood coagulation (tissue factor, plasminogen activator inhibitor-1, and endothelial function (endothelin-1, and endothelin receptors A and B were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF. Results Increased BP and heart rate (HR by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary and blood (systemic were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p Conclusion Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction

  6. Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?

    Science.gov (United States)

    Kelsen, Jesper; Kjaer, Katrine; Chen, Gang; Pedersen, Michael; Røhl, Lisbeth; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Rønn, Lars Christian B

    2006-12-06

    Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition with parecoxib in spontaneously hypertensive rats (SHRs) subjected to transient middle cerebral artery occlusion (tMCAo). Sixty-four male SHRs were randomized to 90 min of intraluminal tMCAo or sham surgery. Parecoxib (10 mg/kg) or isotonic saline was administered intraperitoneally (IP) during the procedure, and twice daily thereafter. Nineteen animals were euthanized after 24 hours, and each hemisphere was examined for mRNA expression of pro-inflammatory cytokines and COX enzymes by quantitative RT-PCR. Twenty-three tMCAo animals were studied with diffusion and T2 weighted MRI within the first 24 hours, and ten of the SHRs underwent follow-up MRI six days later. Thirty-three SHRs were given 5-bromo-2'-deoxy-uridine (BrdU) twice daily on Day 4 to 7 after tMCAo. Animals were euthanized on Day 8 and the brains were studied with free-floating immunohistochemistry for activated microglia (ED-1), hippocampal granule cell BrdU incorporation, and neuronal nuclei (NeuN). Infarct volume estimation was done using the 2D nucleator and Cavalieri principle on NeuN-stained coronal brain sections. The total number of BrdU+ cells in the dentate gyrus (DG) of the hippocampus was estimated using the optical fractionator. We found a significant reduction in infarct volume in parecoxib treated animals one week after tMCAo (p < 0.03). Cortical ADC values in the parecoxib group were markedly less increased on Day 8 (p < 0.01). Interestingly, the parecoxib treated rats were segregated into two subgroups, suggesting a responder vs. non-responder phenomenon. We found indications of mRNA up-regulation of IL-1beta, IL-6, TNF-alpha and COX-2, whereas COX-1 remained unaffected. Hippocampal granule cell BrdU incorporation was not affected by parecoxib treatment. Presence of ED-1+ activated microglia in the hippocampus was related

  7. Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs

    Directory of Open Access Journals (Sweden)

    Peters Annette

    2010-09-01

    Full Text Available Abstract Rationale Several epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR, a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg. Methods 250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter 2.5-AB collected from an urban background site in Augsburg during September and October 2006 (PM2.5 18.2 μg/m3, 10,802 particles/cm3 were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF, blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed. Results Exposure to 1000 μg of PM2.5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP during 2nd-4th day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg and reduced heart rate (HR on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm. BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2 from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2.5-AB instillation results in an activation of endothelin system (endothelin1, renin-angiotensin system (angiotensin converting enzyme and also coagulation system (tissue factor, plasminogen activator inhibitor-1 in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected. Conclusions Our data suggests that high concentrations of PM2.5-AB

  8. Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

    Directory of Open Access Journals (Sweden)

    Vitor E. Valenti

    2013-06-01

    Full Text Available OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY rats and spontaneously hypertensive rats (SH (16 weeks old were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V. The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm. The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus and a depressor dose of sodium nitroprusside (50 μg/kg, bolus. Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05 to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05. CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

  9. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

    DEFF Research Database (Denmark)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

    2017-01-01

    in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...... to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect...... of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague...

  10. Cost-effectiveness of amlodipine compared with valsartan in preventing stroke and myocardial infarction among hypertensive patients in Taiwan

    Directory of Open Access Journals (Sweden)

    Chan L

    2016-05-01

    Full Text Available Lung Chan,1 Chen-Huan Chen,2 Juey-Jen Hwang,3 San-Jou Yeh,4 Kou-Gi Shyu,5 Ruey-Tay Lin,6 Yi-Heng Li,7 Larry Z Liu,8 Jim Z Li,9 Wen-Yi Shau,10 Te-Chang Weng,10 1Department of Neurology, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei, 2Department of Internal Medicine, Faculty of Medicine, National Yang-Ming University, 3Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 4Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, 5Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 6Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, 7Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 8Pfizer Inc, New York, NY, USA; 9Pfizer Inc, San Diego, CA ,USA; 10Pfizer Ltd., New Taipei City, Taiwan Abstract: Hypertension is a major risk factor for strokes and myocardial infarction (MI. Given its effectiveness and safety profile, the calcium channel blocker amlodipine is among the most frequently prescribed antihypertensive drugs. This analysis was conducted to determine the costs and quality-adjusted life years (QALYs associated with the use of amlodipine and valsartan, an angiotensin II receptor blocker, in preventing stroke and MI in Taiwanese hypertensive patients. A state transition (Markov model was developed to compare the 5-year costs and QALYs for amlodipine and valsartan. Effectiveness data were based on the NAGOYA HEART Study, local studies, and a published meta-analysis. Utility data and costs of MI and stroke were retrieved from the published literature. Medical costs were based on the literature and inflated to 2011 prices; drug costs were based on National Health Insurance prices in 2014. A 3% discount rate was used for costs and QALYs and a third-party payer perspective

  11. Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats

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    Julie Carillon

    2016-04-01

    Full Text Available Background: In spontaneously hypertensive rats (SHR, a model of human essential hypertension, oxidative stress is involved in the development of cardiac hypertrophy and fibrosis associated with hypertension. Dietary supplementation with agents exhibiting antioxidant properties could have a beneficial effect in remodeling of the heart. We previously demonstrated a potent anti-hypertrophic effect of a specific melon (Cucumis melo L. concentrate with antioxidant properties in spontaneously hypertensive rats. Relaxin and atrial natriuretic peptide (ANP were reported to reduce collagen deposition and fibrosis progression in various experimental models. Objective: The aim of the present investigation was to test the hypothesis that, beside reduction in oxidative stress, the melon concentrate may act through relaxin, its receptor (relaxin/insulin-like family peptide receptor 1, RXFP1, and ANP in SHR. Design and results: The melon concentrate, given orally during 4 days, reduced cardiomyocyte size (by 25% and totally reversed cardiac collagen content (Sirius red staining in SHR but not in their normotensive controls. Treatment with the melon concentrate lowered cardiac nitrotyrosine-stained area (by 45% and increased by 17–19% the cardiac expression (Western blot of superoxide dismutase (SOD and glutathione peroxidase. In addition, plasma relaxin concentration was normalized while cardiac relaxin (Western blot was lowered in treated SHR. Cardiac relaxin receptor level determined by immunohistochemical analysis increased only in treated SHR. Similarly, the melon concentrate reversed the reduction of plasma ANP concentration and lowered its cardiac expression. Conclusions: The present results demonstrate that reversal of cardiac fibrosis by the melon concentrate involves antioxidant defenses, as well as relaxin and ANP pathways restoration. It is suggested that dietary SOD supplementation could be a useful additional strategy against cardiac hypertrophy

  12. The role of residual blood pressure in antihypertensive effects of captopril treatment in young and adult spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2006-01-01

    Roč. 24, č. S4 (2006), S343-S344 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] R&D Projects: GA MZd(CZ) NR7786 Keywords : blood pressure * captopril * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  13. Home blood pressure monitoring with nurse-led telephone support among patients with hypertension and a history of stroke: a community-based randomized controlled trial.

    Science.gov (United States)

    Kerry, Sally M; Markus, Hugh S; Khong, Teck K; Cloud, Geoffrey C; Tulloch, Jenny; Coster, Denise; Ibison, Judith; Oakeshott, Pippa

    2013-01-08

    Adequate control of blood pressure reduces the risk of recurrent stroke. We conducted a randomized controlled study to determine whether home blood pressure monitoring with nurse-led telephone support would reduce blood pressure in patients with hypertension and a history of stroke. We recruited 381 participants (mean age 72 years) from outpatient and inpatient stroke clinics between Mar. 1, 2007, and Aug. 31, 2009. Nearly half (45%, 170) of the participants had some disability due to stroke. Participants were visited at home for a baseline assessment and randomly allocated to home blood pressure monitoring (n = 187) or usual care (n = 194). Those in the intervention group were given a monitor, brief training and telephone support. Participants who had home blood pressure readings consistently over target (target < 130/80 mm Hg) were advised to consult their family physician. The main outcome measure was a fall in systolic blood pressure after 12 months, measured by an independent researcher unaware of group allocation. Despite more patients in the intervention group than in the control group having changes to antihypertensive treatment during the trial period (60.1% [98/163] v. 47.6% [78/164], p = 0.02), the fall in systolic blood pressure from baseline did not differ significantly between the groups (adjusted mean difference 0.3 mm Hg, 95% confidence interval -3.6 to 4.2 mm Hg). Subgroup analysis showed significant interaction with disability due to stroke (p = 0.03 at 6 months) and baseline blood pressure (p = 0.03 at 12 months). Overall, home monitoring did not improve blood pressure control in patients with hypertension and a history of stroke. It was associated with a fall in systolic pressure in patients who had uncontrolled blood pressure at baseline and those without disability due to stroke. ClinicalTrials.gov registration NCT00514800.

  14. Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke.

    Science.gov (United States)

    Valenti, Vitor E; Abreu, Luiz Carlos de; Fonseca, Fernando L A; Adami, Fernando; Sato, Monica A; Vanderlei, Luiz Carlos M; Ferreira, Lucas Lima; Rodrigues, Luciano M; Ferreira, Celso

    2013-06-01

    Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (peffect of the catalase inhibitor treatment was stronger in the fresh air condition (pcatalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

  15. The pharmacokinetic-pharmacodynamic model of telmisartan and hydrochlorothiazide on blood pressure and plasma potassium after long-term administration in spontaneously hypertensive rats.

    Science.gov (United States)

    Yu, Dan; Chen, Yuancheng; Hao, Kun

    2015-12-01

    A pharmacokinetic-pharmacodynamic model was developed to describe the time course of blood pressure and plasma potassium after long-term telmisartan and/or hydrochlorothiazide administration in spontaneously hypertensive rats. The spontaneously hypertensive rats were administered once daily for 6 weeks. The drug concentration, blood pressure and plasma potassium were monitored for several points. The time courses of blood pressure and plasma potassium were described by indirect response pharmacokinetic-pharmacodynamic model. The synergistic antihypertensive pharmacodynamic interaction between telmisartan and hydrochlorothiazide was observed, which was simulated by the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after co-administration of the two drugs. For plasma potassium, when hydrochlorothiazide administrated alone, the plasma potassium reached to a low steady-state level at 4.64 mmol/L for 6 weeks. The plasma potassium increased to a steady-state level at 4.84 mmol/L after co-administration of telmisartan. The time courses of plasma potassium were successfully characterized by indirect response pharmacokinetic-pharmacodynamic model after long-term administration of telmisartan and/or hydrochlorothiazide. The model captured turnovers of blood pressure and plasma potassium in the different time phases and dose conditions. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: possible implications in hypertension.

    Science.gov (United States)

    Congo Carbajosa, Nadia A; Carbajosa, Nadia A Longo; Corradi, Gerardo; Verrilli, María A Lopez; Guil, María J; Vatta, Marcelo S; Gironacci, Mariela M

    2015-01-01

    Aberrations in the ubiquitin-proteasome system (UPS) are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR) and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86 ± 15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2 ± 8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92 ± 22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7 ± 0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasome activity. Proteasome activity was significantly reduced by 67 ± 4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.

  17. Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: possible implications in hypertension.

    Directory of Open Access Journals (Sweden)

    Nadia A Congo Carbajosa

    Full Text Available Aberrations in the ubiquitin-proteasome system (UPS are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86 ± 15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2 ± 8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92 ± 22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7 ± 0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasome activity. Proteasome activity was significantly reduced by 67 ± 4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.

  18. Echocardiographic estimation of right ventricular stroke work in children with pulmonary arterial hypertension: comparison with invasive measurements.

    Science.gov (United States)

    Di Maria, Michael V; Burkett, Dale A; Younoszai, Adel K; Landeck, Bruce F; Mertens, Luc; Ivy, D Dunbar; Friedberg, Mark K; Hunter, Kendall S

    2015-11-01

    Right ventricular (RV) failure is a key determinant of mortality in children with pulmonary arterial hypertension (PAH). RV stroke work (RVSW) can be estimated as the product of RV systolic pressure and stroke volume. The authors have shown that RVSW predicts adverse outcomes in this population when derived from hemodynamic data; noninvasive assessment of RVSW may be advantageous but has not been assessed. There are few data validating noninvasive versus invasive measurements in children with PAH. The aim of this study was to compare echocardiographically derived RVSW with RVSW determined from hemodynamic data. This was a retrospective study, including subjects with idiopathic PAH and minor or repaired congenital heart disease. Forty-nine subjects were included, in whom cardiac catheterization and echocardiography were performed within 1 month. Fourteen additional patients were included in a separate cohort, in whom catheterization and echocardiography were performed simultaneously. Catheterization-derived RVSW was calculated as RV systolic pressure × (cardiac output/heart rate). Echocardiographically derived RVSW was calculated as 4 × (peak tricuspid regurgitant jet velocity)(2) × (pulmonary valve area × velocity-time integral). Statistics included the intraclass correlation coefficient and Bland-Altman analysis. Echocardiographically derived RVSW was linearly correlated with invasively derived RVSW (r = 0.74, P work was related to indexed pulmonary vascular resistance (r = 0.43, P = .002), tricuspid annular plane systolic excursion (r = 0.41, P = .004), and RV wall thickness (r = 0.62, P work, a potential novel index of RV function, can be estimated noninvasively and is related to pulmonary hemodynamics and other indices of RV performance. Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  19. Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias.

    Science.gov (United States)

    Scridon, Alina; Fouilloux-Meugnier, Emmanuelle; Loizon, Emmanuelle; Rome, Sophie; Julien, Claude; Barrès, Christian; Chevalier, Philippe

    2015-01-01

    The timecourse of left atrial Pitx2 down-regulation in the setting of atrial tachyarrhythmias remains unknown. Accordingly, we aimed to assess the age dependency of left atrial Pitx2 expression in an experimental model of spontaneous atrial tachyarrhythmias in rats. Atrial sampling was performed in three groups (n = 4 each) of young (14-week-old), adult (24-week-old), and ageing (48-week-old) spontaneously hypertensive rats (SHRs), in which we previously demonstrated the age dependency of spontaneous atrial tachyarrhythmias, and three groups (n = 4 each) of age-matched normotensive Wistar-Kyoto (WKY) rats. mRNA expression of Pitx2 was studied using real-time polymerase chain reaction. Ageing SHRs presented significantly lower left atrial Pitx2 expressions compared with age-matched WKY rats (P = 0.02), while no significant difference was observed between young or adult SHRs and age-matched WKY rats (both P > 0.05). Among SHRs, Pitx2 expressions showed a progressive, age-dependent decrease (34.9 ± 6.7 in young SHRs, 17.1 ± 3.6 in adult SHRs, and 10.7 ± 1.7 in ageing SHRs, P = 0.04) and were significantly negatively correlated with both age (Spearman r = -0.86, P Pitx2 down-regulation in SHRs. The strong negative correlation between left atrial Pitx2 expression and heart weight among SHRs may indicate a link between long-standing arterial hypertension and Pitx2-related atrial arrhythmogenicity. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  20. [Serial assessment of myocardial thallium perfusion and fatty acid utilization in spontaneously hypertensive rats: assessment by autoradiography and pin-hole imaging].

    Science.gov (United States)

    Sago, M; Nishimura, T

    1989-07-01

    To evaluate the advantage of free fatty acid imaging on the detection of hypertrophied myocardium, we compared sequentially myocardial thallium and BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) distribution in spontaneously hypertensive rat (SHR) using dual tracer autoradiography and in vivo pin-hole imaging. Autoradiography and pin-hole imaging showed uniform myocardial distribution of BMIPP and thallium within less than 27 weeks age SHR. In 40 weeks age SHR, thallium myocardial distribution showed uniform, however, BMIPP had focal decreases. Quantitative analysis of pin-hole images showed that myocardial BMIPP and thallium uptake ratio decreased according to the ages of SHR. Our data suggest that hypertension is associated with uniform myocardial perfusion and focal alternation in the substrate used for the performance of myocardial work. Based on the above autoradiographic and in vivo pin-hole imagings, I-123 BMIPP imaging may have a potential for early detection on hypertrophic myocardium compared to thallium perfusion in clinically hypertensive patients.

  1. Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study

    Directory of Open Access Journals (Sweden)

    Kawamura Ryoichi

    2009-11-01

    Full Text Available Abstract Background Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD was investigated in a general Japanese population. Methods A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. Results Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002 or ischemic stroke (p Conclusion Elevated serum resistin concentration appears to be an independent risk factor for ischemic stroke, especially lacunar and atherothrombotic infarction in the general Japanese population. The combination of high resistin and the presence of either diabetes or hypertension increased the risk of ischemic stroke.

  2. 42. Hypertension: Morbidity review

    Directory of Open Access Journals (Sweden)

    Hamzullah khan

    2015-10-01

    Conclusions: hypertension is a major modifiable risk factor for coronary artery disease, stroke, eye abnormalities and end stage renal disease, which require proper counseling and management of patients.

  3. Comparative effects of captopril and l-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats.

    Science.gov (United States)

    Miguel-Carrasco, José L; Monserrat, María T; Mate, Alfonso; Vázquez, Carmen M

    2010-04-25

    It has been shown that oxidative stress is involved in the pathogenesis of arterial hypertension. The aim of this work was to study and compare the molecular mechanisms of the antioxidant properties of l-carnitine and captopril in spontaneously hypertensive rats (SHR). Antioxidant enzyme activity/regulation (glutathione peroxidase, glutathione reductase and superoxide dismutase) was measured in the erythrocytes and hearts of SHR. The molecular expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase, angiotensin converting enzyme (ACE), angiotensin II type I receptor (AT(1) receptor) and NF-kappaB/IkappaB system was also measured in the hearts of these animals. Both l-carnitine and captopril augmented the antioxidant defense capacity in SHRs. This effect was mediated by an upregulation of antioxidant enzymes, an increase in the plasma total antioxidant capacity and a reduction of lipid peroxidation and superoxide anion production in the heart. The administration of both compounds to hypertensive animals also produced an upregulation of eNOS and a normalization of ACE, angiotensin AT(1) receptor, and the NF-kappaB/IkappaB system expression. In addition, captopril reduced the arterial blood pressure and the relative heart weights back to control values, whereas l-carnitine caused only a partial reduction of blood pressure values and did not alter the cardiac hypertrophy found in SHRs. In conclusion, we have found that l-carnitine and captopril have a similar antioxidant effect in the hearts of hypertensive rats. The molecular regulation of antioxidant enzymes through an inhibition of the renin-angiotensin system and a modulation of the NF-kappaB/IkappaB system seems to be responsible for this antioxidant effect. 2010 Elsevier B.V. All rights reserved.

  4. Spontaneous coronary artery dissection presenting as an ischaemic stroke in a middle-aged man with anti-cardiolipin antibodies: a case report

    Directory of Open Access Journals (Sweden)

    Lim F

    2010-03-01

    Full Text Available Abstract Introduction Cerebrovascular disease is a major cause of mortality and morbidity worldwide. Ischemic stroke is the most common manifestation, encompassing a wide variety of causative mechanisms. We present the case of a middle-aged male patient with spontaneous coronary artery dissection in the presence of anti-cardiolipin antibodies, leading to left ventricular thrombus and presenting with stroke. Case presentation A 56-year-old Caucasian man presented with dysarthria and right-sided weakness. There was a history of chest pain with autonomic symptoms four days earlier. Examination revealed right-sided hemiparesis. Electrocardiogram showed sinus rhythm with anterior Q waves. Magnetic resonance imaging of the brain showed large left parietal and smaller multiple cerebral infarcts. Echocardiogram showed anterior wall and apical akinesis with a large mural thrombus. Anti-cardiolipin antibodies immunoglobulin G and immunoglobulin M were strongly positive. Coronary angiography showed dissection of the mid left anterior descending artery with normal flow down the distal vessel. He was treated conservatively with anticoagulation and secondary prevention. He was in good health when seen in clinic four months later. Conclusion We highlight the importance of a comprehensive approach at obtaining the correct diagnosis, input of different specialities and the fact that the presence of anti-cardiolipin antibodies is associated with coronary artery dissection in a middle-aged male patient whose presentation was stroke.

  5. Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related

    Czech Academy of Sciences Publication Activity Database

    Janega, P.; Kojšová, S.; Jendeková, L.; Babál, P.; Pecháňová, Olga

    2007-01-01

    Roč. 56, č. 6 (2007), s. 825-828 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : indapamide * myocardial fibrosis * genetic hypertension Subject RIV: ED - Physiology Impact factor: 1.505, year: 2007

  6. Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged Wistar-Kyoto and spontaneously hypertensive rats

    Science.gov (United States)

    This study shows that a single exposure to diesel exhaust causes conduction instability in rats that is worse in the presence of hypertension. The RoR assessment is shown to be a valuable tool that can be used to reveal the deleterious effects of air pollution, particularly in th...

  7. Structural remodeling of resistance vessels and age-dependent antihypertensive effects of captopril treatment in spontaneously hypertensive rats (SHR)

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2006-01-01

    Roč. 22, č. 13 (2006), s. 61-61 ISSN 1000-4718. [International Congress of Pathophysiology /5./. 28.06.2006-01.07.2006, Beijing] R&D Projects: GA MZd(CZ) NR7786 Keywords : hypertensive rat * captopril * vessels Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  8. Function of the isolated perfused kidney in young and adult spontaneously hypertensive and Dahl salt-sensitive rats

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana

    2002-01-01

    Roč. 25, č. 5 (2002), s. 315-321 ISSN 1420-4096 R&D Projects: GA ČR GA306/96/1289; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : rat * hypertension Subject RIV: ED - Physiology Impact factor: 0.968, year: 2002

  9. Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Rebeca Caldeira Machado Berger

    Full Text Available Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%, low salt (LS: 0.03%, and high salt diet (HS: 3% until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.

  10. Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sankar, R.; Domer, F.R.; Taylor, B.

    1982-01-01

    Researchers have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure

  11. Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats.

    Science.gov (United States)

    Negoro, N; Kanayama, Y; Iwai, J; Umetani, N; Nishimura, M; Konishi, Y; Okamura, M; Inoue, T; Takeda, T

    1994-04-12

    To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

  12. Parameter estimation of feedback gain in a stochastic model of renal hemodynamics: differences between spontaneously hypertensive and Sprague-Dawley rats

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Yip, Kay-Pong; Marsh, Donald J

    2006-01-01

    Proximal tubular pressure shows periodic self-sustained oscillations in normotensive rats but highly irregular fluctuations in spontaneously hypertensive rats (SHR). Although we have suggested that the irregular fluctuations in SHR represent low-dimensional deterministic chaos in tubuloglomerular...... mechanisms not included explicitly in the model. In its deterministic version, the model can have chaotic dynamics arising from TGF. The model introduces random fluctuations into a parameter that determines the gain of TGF. The model shows a rich variety of dynamics ranging from low-dimensional deterministic...... oscillations and chaos to high-dimensional random fluctuations. To fit the data from normotensive rats, the model must introduce only a small variation in the feedback gain, and its estimates of that gain agree well with experimental values. These results support the use of the deterministic model of nephron...

  13. Comparison of the sagittal sinus cross-sectional area between patients with multiple sclerosis, hydrocephalus, intracranial hypertension and spontaneous intracranial hypotension: a surrogate marker of venous transmural pressure?

    Science.gov (United States)

    Bateman, Grant A; Lechner-Scott, Jeannette; Copping, Ross; Moeskops, Christopher; Yap, Swee Leong

    2017-07-06

    There is evidence that patients with multiple sclerosis (MS) and hydrocephalus share some common pathophysiological mechanisms. Alterations in CSF pressure are known to affect cerebral venous sinus geometry. To further explore these mechanisms, we measured the superior sagittal sinus (SSS) cross-sectional area 3 cm above the torcular using T2 images in 20 MS, 10 spontaneous intracranial hypotension (SIH), 21 hydrocephalus and 20 idiopathic intracranial hypertension (IIH) patients and compared with 20 matched controls. The SSS area was reduced by 25% in hydrocephalus (p = 0.0008), increased by 22% (p = 0.037) in SIH and unchanged in IIH compared to matched controls. In MS there was a 16% increase in SSS area (p = 0.01).The findings suggest that changes in SSS cross-sectional are common between MS and SIH patients, while in hydrocephalus and IIH these are different.

  14. Mn++-stimulated 3H-inositol incorporation in cultured vascular smooth muscle cells: deficiency in cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Buck, S.H.; Nabika, T.; Lovenberg, W.

    1985-01-01

    Incubation of cultured dissociated aortic smooth muscle cells from Wistar-Kyoto rats (WKY) with Mn++ resulted in a 10-fold stimulation of 3 H-myo-inositol incorporation into membrane phospholipids. The stimulation was temperature and energy dependent. The Mn++ EC50 was 1 mM and maximum stimulation occurred at 10 mM Mn++. Other cations were ineffective. In cells from spontaneously hypertensive rats (SHR), the Mn++ EC50 was unchanged whereas the maximum stimulation of 3 H-inositol incorporation was reduced by 50% compared to cells from parallel WKY cultures. These results suggest that in SHR cultured vascular smooth muscle cells there is a deficiency in an enzymatic process mediating exchange of free inositol with the headgroup inositol of membrane phosphatidylinositol

  15. Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

    Science.gov (United States)

    Nováková, Marta; Parkanová, Daniela; Sumová, Alena

    2013-01-01

    The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF) leads to the development of food anticipatory activity (FAA) and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR). The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase), in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock. PMID:24086613

  16. Increased sensitivity of the circadian system to temporal changes in the feeding regime of spontaneously hypertensive rats - a potential role for Bmal2 in the liver.

    Directory of Open Access Journals (Sweden)

    Lenka Polidarová

    Full Text Available The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF leads to the development of food anticipatory activity (FAA and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR. The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase, in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock.

  17. Healthy lifestyle factors and risk of cardiovascular events and mortality in treatment-resistant hypertension: the Reasons for Geographic and Racial Differences in Stroke study.

    Science.gov (United States)

    Diaz, Keith M; Booth, John N; Calhoun, David A; Irvin, Marguerite R; Howard, George; Safford, Monika M; Muntner, Paul; Shimbo, Daichi

    2014-09-01

    Few data exist on whether healthy lifestyle factors are associated with better prognosis among individuals with apparent treatment-resistant hypertension, a high-risk phenotype of hypertension. The purpose of this study was to assess the association of healthy lifestyle factors with cardiovascular events, all-cause mortality, and cardiovascular mortality among individuals with apparent treatment-resistant hypertension. We studied participants (n=2043) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with apparent treatment-resistant hypertension (blood pressure ≥140/90 mm Hg despite the use of 3 antihypertensive medication classes or the use of ≥4 classes of antihypertensive medication regardless of blood pressure control). Six healthy lifestyle factors adapted from guidelines for the management of hypertension (normal waist circumference, physical activity ≥4 times/week, nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension diet score, and low sodium-to-potassium intake ratio) were examined. A greater number of healthy lifestyle factors were associated with lower risk for cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable-adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle factors were 0.91 (0.68-1.21), 0.80 (0.57-1.14), and 0.63 (0.41-0.95), respectively (P-trend=0.020). Physical activity and nonsmoking were individual healthy lifestyle factors significantly associated with lower risk for cardiovascular events. Similar associations were observed between healthy lifestyle factors and risk for all-cause and cardiovascular mortality. In conclusion, healthy lifestyle factors, particularly physical activity and nonsmoking, are associated with a lower risk for cardiovascular events and mortality among individuals with apparent treatment

  18. Inactivation of Gi proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Zemančíková, A.; Török, J.; Zicha, Josef; Kuneš, Jaroslav

    2008-01-01

    Roč. 57, č. 2 (2008), s. 299-302 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:VEGA(SK) 2/6150/27 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * adrenergic vasoconstriction * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

  19. Pertussis toxin-sensitive alpha-adrenergic modulation of voltage - dependent calcium channels in spontaneously hypertensive rats (SHR)

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Dobešová, Zdenka; Líšková, Silvia; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S6 (2006), s. 34-34 ISSN 0263-6352. [Scientific Meeting of the International Society of Hypertension /21./. 15.10.2006-19.10.2006, Fukuoka] R&D Projects: GA MZd(CZ) NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * alpha adrenergic vasoconstriction * voltage-dependent calcium channels * SHR rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  20. Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

    Science.gov (United States)

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-01-01

    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

  1. Angiotensin-(1-7) Blockade Attenuates Captopril- or Hydralazine-Induced Cardiovascular Protection in Spontaneously Hypertensive Rats-Treated with L-NAME

    Science.gov (United States)

    Benter, Ibrahim F.; Yousif, Mariam H. M.; Al-Saleh, Fatemah M.; Chappell, Raj Raghupathy Mark C.; Diz, Debra I.

    2011-01-01

    We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHR) chronically treated with the nitric oxide synthesis inhibitor L-NAME (SHR-L). L-NAME (80 mg/L) administration for three weeks increased mean arterial pressure (MAP) from 196 ± 6 mmHg to 229 ± 3 mmHg (pcaptopril (300 mg/L in drinking water) or hydralazine (1.5 mg/kg/day ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment, and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-L hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery following ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role to effectively buffer the increase in blood pressure and renal injury, as well as the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage. PMID:21326110

  2. Radiogenic changes in the behavior and physiology of the spontaneously hypertensive rat: evidence for a dissociation between acute hypotension and incapacitation

    International Nuclear Information System (INIS)

    Mickley, G.A.; Teitelbaum, H.; Parker, G.A.; Vieras, F.; Dennison, B.A.; Bonney, C.H.

    1982-01-01

    Immediately following exposure to a sufficiently large dose of ionizing radiation, rats and several other species experience a transient period of acute hypotension and an accompanying deficit in performance. Although significant correlations have been reported between the drop in blood pressure and the early transient incapacitation (ETI) and a causal relationship has been suggested, the extent to which hypotension precipitates the occurrence of the behavioral deficits remains uncertain. The present experiments investigated both radiogenic blood pressure and performance changes in a strain of rat bred for hypertension (spontaneously hypertensive rat: SHR) in order to determine if high blood pressure might attenuate ETI. Although male SHRs experienced a severe ETI and a drop in blood pressure, much of the data is inconsistent with the hypothesis that hypotension causes performance decrements. In an additional series of studies, blood volume and serum chemistry data were analyzed. Male SHRs were significantly higher than normotensive controls on several blood chemistry determinations. Exposure to ionizing radiation, more often than not, enhanced these differences. These results could not be explained on the basis of radiogenic blood volume fluctuations

  3. Long-Term Regulation of the Local Renin-Angiotensin System in the Myocardium of Spontaneously Hypertensive Rats by Feeding Bioactive Peptides Derived from Spirulina platensis.

    Science.gov (United States)

    Pan, Huanglei; She, Xingxing; Wu, Hongli; Ma, Jun; Ren, Difeng; Lu, Jun

    2015-09-09

    This study investigated the long-term (8 weeks) anti-hypertensive effects of 10 mg/kg tripeptides isolated from Spirulina platensis, Ile-Gln-Pro (IQP) and Val-Glu-Pro (VEP), and S. platensis hydrolysates (SH) on spontaneously hypertensive rats. The treatment period was 6 weeks, and observation continued for another 2 weeks. After treatment, weighted systolic blood pressure, weighted diastolic blood pressure, left ventricular mass index, and right ventricular mass index of groups treated with IQP, VEP, and SH were significantly lower than those of the group treated with distilled water, even when the treatments had been withdrawn for 2 weeks. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting showed the mRNA expression levels and protein/peptide concentrations of the main components of the renin angiotensin system in myocardium were significantly affected by treatment: angiotensin converting enzyme, angiotensin II, and angiotensin type 1 receptor were down-regulated, whereas angiotensin type 2 receptor, angiotensin converting enzyme 2, angiotensin-(1-7), and Mas receptor were up-regulated.

  4. Delayed perfusion phenomenon in a rat stroke model at 1.5 T MR: An imaging sign parallel to spontaneous reperfusion and ischemic penumbra?

    Energy Technology Data Exchange (ETDEWEB)

    Chen Feng [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Radiology, Zhong Da Hospital, Southeast University, 87 Ding Jia Qiao Road, Nanjing 210009, Jiangsu Province (China); Suzuki, Yasuhiro [Department of Molecular and Cellular Medicine, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu (Japan); Nagai, Nobuo [Department of Molecular and Cellular Medicine, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Sun Xihe [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Radiology, the Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province (China); Coudyzer, Walter [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Yu Jie [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Marchal, Guy [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Ni Yicheng [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium)]. E-mail: Yicheng.Ni@med.kuleuven.ac.be

    2007-01-15

    Introduction: Delayed perfusion (DP) sign at MR imaging was reported in stroke patients. We sought to experimentally elucidate its relation to spontaneous reperfusion and ischemic penumbra. Methods: Stroke was induced by photothrombotic occlusion of middle cerebral artery in eight rats and studied up to 72 h using a 1.5 T MR scanner with T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI). Relative signal intensity (rSI), relative lesion volume (rLV), relative cerebral blood flow (rCBF), PWI{sub rLV}-DWI{sub rLV} mismatch (penumbra) and DP{sub rLV} were quantified and correlated with neurological deficit score (NDS), triphenyl tetrazolium chloride (TTC) staining, microangiography (MA) and histopathology. Results: The rSI and rLV characterized this stroke model on different MRI sequences and time points. DSC-PWI reproduced cortical DP in all rats, where rCBF evolved from 88.9% at 1 h through 64.9% at 6 h to 136.3% at 72 h. The PWI{sub rLV}-DWI{sub rLV} mismatch reached 10 {+-} 5.4% at 1 h, remained positive through 12 h and decreased to -3.3 {+-} 4.5% at 72 h. The incidence and rLV of the DP were well correlated with those of the penumbra (p < 0.01, r {sup 2} = 0.85 and p < 0.0001, r {sup 2} = 0.96, respectively). Shorter DP durations and more collateral arterioles occurred in rats without (n = 4) than with (n = 4) cortex involvement (p < 0.05). Rats without cortex involvement tended to earlier reperfusion and a lower NDS. Microscopy confirmed MRI, MA and TTC findings. Conclusions: In this rat stroke model, we reproduced clinically observed DP on DSC-PWI, confirmed spontaneous reperfusion, and identified the penumbra extending to 12 h post-ischemia, which appeared interrelated.

  5. The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Wachtell, K.; Devereux, R.B.; Lyle, P.A.

    2008-01-01

    The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment...

  6. BLOCKADE OF ROSTRAL VENTROLATERAL MEDULLA (RVLM BOMBESIN RECEPTOR TYPE 1 DECREASES BLOOD PRESSURE AND SYMPATHETIC ACTIVITY IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Izabella Silva De Jesus Pinto

    2016-06-01

    Full Text Available IIntrathecal injection of bombesin (BBS promoted hypertensive and sympathoexcitatory effects in normotensive (NT rats. However, the involvement of rostral ventrolateral medulla (RVLM in these responses is still unclear. In the present study, we investigated: (1 the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR; (2 the contribution of RVLM bombesin type 1 receptors (BB1 to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v. were instrumented to record mean arterial pressure (MAP, diaphragm (DIA motor and renal sympathetic nerve activity (RSNA. In NT rats and SHR, BBS (0.3 mM nanoinjected into RVLM increased MAP (33.9 ± 6.6 mmHg and 37.1 ± 4.5 mmHg, respectively; p < 0.05 and RSNA (97.8 ± 12.9 % and 84.5 ± 18.1 %, respectively; p < 0.05. In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7 %; p < 0.05. BB1 receptors antagonist (BIM-23127; 3 mM reduced MAP (-19.9 ± 4.4 mmHg; p < 0.05 and RSNA (-17.7 ± 3.8 %; p < 0.05 in SHR, but not in NT rats (-2.5 ± 2.8 mmHg; -2.7 ± 5.6 %, respectively. These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

  7. Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats.

    Science.gov (United States)

    Girgih, Abraham T; Alashi, Adeola; He, Rong; Malomo, Sunday; Aluko, Rotimi E

    2014-08-01

    This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined. Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0% levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase). Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly (p < 0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054 μg/mL) when compared to control rats that were fed only with casein (0.151 μg/mL). The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.

  8. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

    Science.gov (United States)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

    2017-12-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  9. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

    Directory of Open Access Journals (Sweden)

    Dervola Kine S

    2012-12-01

    Full Text Available Abstract Background Previous reports suggest that omega-3 (n-3 polyunsaturated fatty acids (PUFA supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR. SHR dams were given n-3 PUFA (EPA and DHA-enriched feed (n-6/n-3 of 1:2.7 during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY control rats were given control-feed (n-6/n-3 of 7:1. During postnatal days (PND 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms

  10. Hypertension og hjernen

    DEFF Research Database (Denmark)

    Christensen, Hanne; Strandgaard, Svend

    2009-01-01

    Hypertension is a major and modifiable risk factor of stroke and dementia. Hypertension causes remodelling of the cerebral resistance vessels, impairing their tolerance to very low blood pressure. In primary prevention of stroke, the effect of beta-blockers is inferior to other classes...

  11. Selective replacement of mitochondrial DNA increases the cardioprotective effect of chronic continuous hypoxia in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Neckář, Jan; Svatoňová, Anna; Weissová, Romana; Drahota, Zdeněk; Zajíčková, Pavlína; Brabcová, I.; Kolář, D.; Alánová, Petra; Vašinová, Jana; Šilhavý, Jan; Hlaváčková, Markéta; Tauchmannová, Kateřina; Milerová, Marie; Ošťádal, Bohuslav; Červenka, L.; Žurmanová, J.; Kalous, M.; Nováková, Olga; Novotný, J.; Pravenec, Michal; Kolář, František

    2017-01-01

    Roč. 131, č. 9 (2017), s. 865-881 ISSN 0143-5221 R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : chronic hypoxia * heart * hypertension * ischaemia–reperfusion injury * mitochondrial genome * mitochondrial permeability transition pore Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Physiology (including cytology) Impact factor: 4.936, year: 2016

  12. Three-dimensional echocardiographic ventricular mass/end-diastolic volume ratio in native hypertensive patients: relation between stroke volume and geometry.

    Science.gov (United States)

    Lembo, Maria; Esposito, Roberta; Santoro, Ciro; Lo Iudice, Francesco; Schiano-Lomoriello, Vincenzo; Fazio, Valeria; Grimaldi, Maria Gabriella; Trimarco, Bruno; de Simone, Giovanni; Galderisi, Maurizio

    2018-03-22

    Elevated left ventricular (LV) mass/end-diastolic volume ratio (LVM/EDV) has been associated with higher evidence of myocardial fibrosis and dysfunction in hypertensive patients by cardiac magnetic resonance, a technique with limited availability. We investigated the ability of three-dimensional (3D) echocardiography in identifying a phenotype of LV concentric geometry according to LVM/EDV ratio, possibly detecting early myocardial damage in native-hypertensive patients. One hundred and twenty-eight native-hypertensive patients underwent 2D and 3D-echocardiography. The population was divided into two groups, according to cut-off point values of 3D-LVM/EDV ratio corresponding to its upper 95% confidence interval in a population of 90 healthy normotensive individuals: LVM/EDV ratio cut-off was 1.22 in men and 1.23 in women. An increased 3D-LVM/EDV ratio identified a higher rate of LV concentric geometry in comparison with 2D-derived relative wall thickness (37 versus 24%, P = 0.03). Patients with LVM/EDV ratio of 1.22 or more in men and 1.23 or more in women were significantly older, had smaller 3D-LV end-diastolic and end-systolic volumes and higher LV mass index, without difference in ejection fraction. 3D-stroke volume (P geometry than 2D-relative wall thickness. Stroke volume is independently and negatively associated with LVM/EDV ratio and its reduction represents an early marker of myocardial dysfunction in hypertensives with LV concentric geometry.

  13. Effect of Clonidine (an Antihypertensive Drug Treatment on Oxidative Stress Markers in the Heart of Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Nik Syamimi Nik Yusoff

    2013-01-01

    Full Text Available Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C, SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME]. Rats (SHRC were administered with Clonidine (0.5 mg kg−1 day−1 from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg−1 day−1 from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS (P<0.001 and reduced the thibarbituric acid reactive substances (TBARS (P<0.001 and protein carbonyl content (PCO (P<0.05. These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME.

  14. Effect of Olea europea L. leaf extract on haemodynamic status and lipid peroxidation in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Miloradović Zoran

    2013-01-01

    Full Text Available Hypertension is one of the main causes of cardiovascular disorders and since ancient times olive tree leaves have been used in its therapy. However the mechanisms of their atihypertensive effect have not been sufficiently explained yet. The main objective of our study was to investigate acute effect of olive tree leaves extract on haemodynamics and lipid peroxidation in rats with congenital hypertension under normal and blocked synthesis of nitric oxide. For the purpose of our research, there were used olive tree leaf extract EFLA® 943 as well as inhibitor of nitric oxide synthase enzyme L-NAME. Nitric oxide synthesis inhibition led to statistically significant increase of mean arterial pressure, reducing heart rate and cardiac output, increase of total vascular resistance and lipid peroxidation in plasma. Treatment by olive leaf extract led to decrease of mean arterial pressure, reducing the frequency and cardiac output, without change in lipid peroxidation. Olive leaf extract under blockade of nitric oxide led to decrease of mean arterial pressure, total peripheral resistance remained high, cardiac output low, and lipid peroxidation significantly increased. General conclusion is that olive leaf extract has a strong antihypertensive effect, decreases cardiac pre and after load and does not influence lipid peroxidation. Under blockade of nitric oxide synthesis, this extract keeps antihypertensive properties, but due to strong endothelial dysfunction, it is unable to regulate increased total peripheral resistance and marked lipid peroxidation. [Projekat Ministarstva nauke Republike Srbije, br. 175096: Ispitivanje antihipertenzivnog potencijala supstanci prirodnog i sintetskog porekla u eksperimentalnim modelima kardiovaskularnih i bubrežnih oboljenja

  15. Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats.

    Science.gov (United States)

    Varagic, Jasmina; Ahmad, Sarfaraz; Voncannon, Jessica L; Moniwa, Norihito; Simington, Stephen W; Brosnihan, Bridget K; Gallagher, Patricia E; Habibi, Javad; Sowers, James R; Ferrario, Carlos M

    2012-09-01

    Increased sympathetic outflow, renin-angiotensin system (RAS) activity, and oxidative stress are critical mechanisms underlying the adverse cardiovascular effects of dietary salt excess. Nebivolol is a third-generation, highly selective β1-receptor blocker with RAS-reducing effects and additional antioxidant properties. This study evaluated the hypothesis that nebivolol reduces salt-induced cardiac remodeling and dysfunction in spontaneous hypertensive rats (SHRs) by suppressing cardiac RAS and oxidative stress. Male SHRs (8 weeks of age) were given an 8% high salt diet (HSD; n = 22), whereas their age-matched controls (n = 10) received standard chow. In a subgroup of HSD rats (n = 11), nebivolol was given at a dose of 10 mg/kg per day by gastric gavage. After 5 weeks, HSD exacerbated hypertension as well as increased left-ventricular weight and collagen deposition while impairing left-ventricular relaxation. Salt-induced cardiac remodeling and dysfunction were associated with increased plasma renin concentration (PRC), cardiac angiotensin II immunostaining, and angiotensin-converting enzyme (ACE)/ACE2 mRNA and activity ratio. HSD also increased cardiac 3-nitrotyrosine staining indicating enhanced oxidative stress. Nebivolol treatment did not alter the salt-induced increase in arterial pressure, left-ventricular weight, and cardiac dysfunction but reduced PRC, cardiac angiotensin II immunostaining, ACE/ACE2 ratio, oxidative stress, and fibrosis. Our data suggest that nebivolol, in a blood pressure-independent manner, ameliorated cardiac oxidative stress and associated fibrosis in salt-loaded SHRs. The beneficial effects of nebivolol may be attributed, at least in part, to the decreased ACE/ACE2 ratio and consequent reduction of cardiac angiotensin II levels.

  16. Super, red palm and palm oleins improve the blood pressure, heart size, aortic media thickness and lipid profile in spontaneously hypertensive rats.

    Science.gov (United States)

    Boon, Chee-Meng; Ng, Mei-Han; Choo, Yuen-May; Mok, Shiueh-Lian

    2013-01-01

    Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension. Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (prats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR. The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR.

  17. The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Dalpiaz, P.L.M.; Lamas, A.Z.; Caliman, I.F. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Medeiros, A.R.S. [Ciências Biológicas e da Saúde, Instituto Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Andrade, T.U. [Departamento de Farmácia, Centro Universitário de Vila Velha, Vila Velha, ES (Brazil); Alves, M.F.; Carmona, A.K. [Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Bissoli, N.S. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2013-02-01

    Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

  18. Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

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    Kanintra Suwanmanon

    2014-12-01

    Full Text Available In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY rats were randomized into seven groups. Until the 8th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD; Group 2, medium dose of GABA and nattokinase in the SHR (SMD; Group 3, low dose of GABA and nattokinase in the SHR (SLD; Group 4, negative control in the SHR (SD; Group 5, positive control in the SHR (SM; Group 6, high dose of GABA and nattokinase in the WKY (WHD; and Group 7, negative control in the WKY (WD. Distilled water served as the negative control, and captopril (50 mg/kg, a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8th week to the 16th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.

  19. Effects of Acidic Polysaccharides from Gastrodia Rhizome on Systolic Blood Pressure and Serum Lipid Concentrations in Spontaneously Hypertensive Rats Fed a High-Fat Diet

    Science.gov (United States)

    Lee, Ok-Hwan; Kim, Kyung-Im; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

    2012-01-01

    The effects of acidic polysaccharides purified from Gastrodia rhizome on blood pressure and serum lipid levels in spontaneously hypertensive rats (SHR) fed a high-fat diet were investigated. Acidic polysaccharides were purified from crude polysaccharides by DEAE-Sepharose CL-6B. Thirty-six male SHR were randomly divided into three groups: Gastrodia rhizome crude polysaccharide (A), acidic polysaccharide (B) groups, and a control group (C). A 5-week oral administration of all treatment groups was performed daily in 3- to 8-week-old SHRs with a dose of 6 mg/kg of body weight/day. After 5 weeks of treatment, total cholesterol in the acidic polysaccharide group, at 69.7 ± 10.6 mg/dL, was lower than in the crude polysaccharide group (75.0 ± 6.0 mg/dL) and the control group (89.2 ± 7.4 mg/dL). In addition, triglyceride and low-density lipoprotein cholesterol levels in the acidic polysaccharide group were lower than in the crude polysaccharide and control groups. The atherogenic index of the acidic polysaccharide group was 46.3% lower than in the control group. Initial blood pressure after the initial three weeks on the high-fat diet averaged 195.9 ± 3.3 mmHg among all rats. Compared with the initial blood pressure, the final blood pressure in the control group was increased by 22.8 mmHg, whereas it decreased in the acidic polysaccharide group by 14.9 mmHg. These results indicate that acidic polysaccharides from Gastrodia rhizome reduce hypertension and improve serum lipid levels. PMID:22312280

  20. Long-term effect of prazosin administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats.

    Science.gov (United States)

    Kristek, F; Koprdova, R

    2011-06-01

    The sympathetic nervous system belongs to the essential systems participating in blood pressure (BP) regulation. Inhibitory intervention into the key point of its operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously hypertensive rats (SHR) might affect the development of the hypertension in later ontogenic periods. We studied the long-term effect of prazosin administration on the cardiovascular system of young Wistar rats and SHR. Four-week-old animals were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10 mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the plethysmographic method. After six weeks under anaesthesia, the carotid artery was cannulated for BP registration, and the jugular vein was cannulated for administration of drugs. Afterwards, the animals were perfused with a glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left descending coronary artery was processed using electron microscopy. The prazosin administration evoked the following results in both groups: a decrease of BP and heart/body weight ratio, enhancement of hypotensive responses to acetylcholine (0.1 μg, 1 μg, and 10 μg), and an increase in the inner diameter of the coronary artery without changes in wall thickness, cross sectional area (CSA) (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In the SHR group, a reduction was observed in BP increase after noradrenaline (1 μg) application. CSA of endothelial cells which was decreased in the SHR (compared to the control Wistar rats) was increased after prazosin treatment (up to control value). Long-term prazosin administration from early ontogeny partially prevented some pathological alterations in the cardiovascular system of SHR.

  1. Rat middle cerebral artery occlusion is not a suitable model for the study of stroke-induced spontaneous infections.

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    Mireia Campos-Martorell

    Full Text Available BACKGROUND: Infections related to stroke-induced immunodepression are an important complication causing a high rate of death in patients. Several experimental studies in mouse stroke models have described this process but it has never been tested in other species such as rats. METHODS: Our study focused on the appearance of secondary systemic and pulmonary infections in ischemic rats, comparing with sham and naive animals. For that purpose, male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO or to transient MCAO (tMCAO inserting a nylon filament. Forty-eight hours after ischemia, blood and lung samples were evaluated. RESULTS: In eMCAO set, ischemic rats showed a significant decrease in blood-peripheral lymphocytes (naive = 58.8±18.1%, ischemic = 22.9±16.4% together with an increase in polymorphonuclears (PMNs (naive = 29.2±14.7%, ischemic = 71.7±19.5%, while no change in monocytes was observed. The increase in PMNs counts was positively correlated with worse neurological outcome 48 hours after eMCAO (r = 0.55, p = 0.043. However, sham animals showed similar changes in peripheral leukocytes as those seen in ischemic rats (lymphocytes: 40.1±19.7%; PMNs: 51.7±19.2%. Analysis of bacteriological lung growth showed clear differences between naive (0±0 CFU/mL; log10 and both sham (3.9±2.5 CFU/mL; log10 and ischemic (4.3±2.9 CFU/mL; log10 groups. Additionally, naive animals presented non-pathological lung histology, while both sham and ischemic showed congestion, edema or hemorrhage. Concordant results were found in the second set of animals submitted to a tMCAO. CONCLUSIONS: Inflammatory and infection changes in Wistar rats subjected to MCAO models may be attributed not only to the brain ischemic injury but to the surgical aggression and/or anaesthetic stress. Consequently, we suggest that stroke-induced immunodepression in ischemic experimental models should be interpreted with caution

  2. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

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    Danijela Karanovic

    Full Text Available Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD. Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger or losartan (angiotensin II type 1 receptor blocker treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS, erythrocyte antioxidant enzymes activities and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities, kidney function and structure in spontaneously hypertensive rats (SHR with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v. twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day, tempol (T,100 mg/kg/day or combined T+L treatment (by gavage during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1 protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4 protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2 protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria, pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  3. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

    Science.gov (United States)

    Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  4. Effect of Clonidine (an antihypertensive drug) treatment on oxidative stress markers in the heart of spontaneously hypertensive rats.

    Science.gov (United States)

    Nik Yusoff, Nik Syamimi; Mustapha, Zulkarnain; Govindasamy, Chandran; Sirajudeen, K N S

    2013-01-01

    Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO) in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C), SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME)]. Rats (SHRC) were administered with Clonidine (0.5 mg kg(-1) day(-1)) from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg(-1) day(-1)) from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP) was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS) (P heart of SHR and SHR+L-NAME.

  5. A case of progressive hypertension preceding gemcitabine-associated thrombotic microangiopathy complicated by acute kidney injury and stroke.

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2009-01-01

    Gemcitabine-associated thrombotic microangiopathy is being increasingly recognized as a serious complication of treatment. We report a normotensive patient who developed progressive hypertension after commencing gemcitabine therapy. She also developed subtle changes in her platelet count and serum creatinine months before her emergent presentation. Clinicians should be aware of new onset or worsening hypertension and \\'mild\\' biochemical changes in gemcitabine-treated patients.

  6. Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in spontaneously hypertensive rats on high-salt diet in a blood-pressure-independent manner.

    Science.gov (United States)

    Trenkner, Jörg; Priem, Friedrich; Bauer, Christian; Neumayer, Hans-Hellmut; Raschak, Manfred; Hocher, Berthold

    2002-08-01

    The renal endothelin (ET) system is involved in the pathogenesis of kidney fibrosis as well as blood pressure control by regulating tubular sodium excretion. Long-term effects of ETA receptor blockade on blood pressure and kidney function in spontaneously hypertensive rats (SHRs) on a high-salt diet are unknown. We treated SHRs on a 6% (w/v) NaCl sodium diet (SHR-S) for 48 weeks with the ETA antagonist LU 135252 (whose selectivity for ETA is 150 times greater than for ETB) with 10, 30 and 100 mg x kg(-1) x day(-1) or placebo. The ETA antagonist had at no time-point any effect on blood pressure. Glomerular filtration rate was normal in SHR-S and not altered by LU 135252. However, urinary albumin excretion was markedly reduced by the ETA antagonist (SHR-S, 145+/-50 mg/day; SHR-S+10 mg x kg(-1) x day(-1) LU 135252, 33+/-11 mg/day, Pproteinuria-induced chronic renal failure.

  7. Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats.

    Science.gov (United States)

    Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

    2017-01-01

    Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway.

  8. Long-Term Stimulation with Electroacupuncture at DU20 and ST36 Rescues Hippocampal Neuron through Attenuating Cerebral Blood Flow in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Gui-Hua Tian

    2013-01-01

    Full Text Available This study was designed to investigate the effect of long-term electroacupuncture at Baihui (DU20 and Zusanli (ST36 on cerebral microvessels and neurons in CA1 region of hippocampus in spontaneously hypertensive rats (SHR. A total of 45 male Wistar rats and 45 SHR were randomly grouped, with or without electroacupuncture (EA at DU20 and ST36, once every other day for a period of 8 weeks. The mean arterial pressure (MAP was measured once every 2 weeks. Cerebral blood flow (CBF and the number of open microvessels in hippocampal CA1 region were detected by Laser Doppler and immunohistochemistry, respectively. Nissl staining and Western blotting were performed, respectively, to determine hippocampus morphology and proteins that were implicated in the concerning signaling pathways. The results showed that the MAP in SHR increased linearly over the observation period and was significantly reduced following electroacupuncture as compared with sham control SHR rats, while no difference was observed in Wistar rats between EA and sham control. The CBF, learning and memory capacity, and capillary rarefaction of SHR were improved by EA. The upregulation of angiotensin II type I receptor (AT1R, endothelin receptor (ETAR, and endothelin-1 (ET-1 in SHR rats was attenuated by electroacupuncture, suggesting an implication of AT1R, ETAR, and ET-1 pathway in the effect of EA.

  9. Sex-Differences in Renal Expression of Selected Transporters and Transcription Factors in Lean and Obese Zucker Spontaneously Hypertensive Fatty Rats

    Directory of Open Access Journals (Sweden)

    Andrea Babelova

    2015-01-01

    Full Text Available The aim of this study was to identify sex-dependent expression of renal transporter mRNA in lean and obese Zucker spontaneously hypertensive fatty (ZSF1 rats and to investigate the interaction of the most altered transporter, organic anion transporter 2 (Oat2, with diabetes-relevant metabolites and drugs. Higher incidence of glomerulosclerosis, tubulointerstitial fibrosis, and protein casts in Bowman’s space and tubular lumen was detected by PAS staining in obese male compared to female ZSF1 rats. Real-time PCR on RNA isolated from kidney cortex revealed that Sglt1-2, Oat1-3, and Oct1 were higher expressed in kidneys of lean females. Oct2 and Mrp2 were higher expressed in obese males. Renal mRNA levels of transporters were reduced with diabetic nephropathy in females and the expression of transcription factors Hnf1β and Hnf4α in both sexes. The highest difference between lean and obese ZSF1 rats was found for Oat2. Therefore, we have tested the interaction of human OAT2 with various substances using tritium-labeled cGMP. Human OAT2 showed no interaction with diabetes-related metabolites, diabetic drugs, and ACE-inhibitors. However, OAT2-dependent uptake of cGMP was inhibited by furosemide. The strongly decreased expression of Oat2 and other transporters in female diabetic ZSF1 rats could possibly impair renal drug excretion, for example, of furosemide.

  10. Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

    Science.gov (United States)

    Zhou, Ziyi; Li, Jianping; Yu, Yaren; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Mingli; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Delu; Huang, Xiao; Cheng, Xiaoshu; Wang, Binyan; Hou, Fan Fan; Wang, Xiaobin; Qin, Xianhui; Huo, Yong

    2018-01-01

    We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

  11. Lifestyle modifications to prevent and control hypertension. 7. Recommendations on stress management. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada.

    Science.gov (United States)

    Spence, J D; Barnett, P A; Linden, W; Ramsden, V; Taenzer, P

    1999-05-04

    . Individualized cognitive behavioural interventions are more likely to be effective than single-component interventions. These recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth International Conference on Preventive Cardiology. They have not been clinically tested. The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.

  12. Manejo da hipertensão arterial na isquemia cerebral aguda Management of arterial hypertension in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    WALTER JOSÉ FAGUNDES-PEREYRA

    1999-12-01

    Full Text Available OBJETIVO: Avaliar o nível de conhecimento dos médicos, através de sua conduta, em paciente com quadro de hipertensão arterial na fase aguda da isquemia cerebral. Também comentamos as principais condutas nesta fase, com ênfase na tensão arterial (TA. MÉTODO: Foram entrevistados 120 médicos da clínica médica e da cirurgia geral, em dez dos maiores Hospitais de Belo Horizonte, em 1997. Todos responderam a um questionário contendo um caso clínico de paciente hipertenso leve, admitido com quadro de isquemia cerebral e tensão arterial de 186x110 mmHg. Os profissionais deveriam optar por reduzir, aumentar ou manter a TA. RESULTADOS: Dos entrevistados, 38 (31,7% responderam que reduziriam os níveis tensionais, 82 (68,3% optaram pela manutenção e nenhum aumentaria (pPURPOSE: We aimed with study to assess the current clinical practice about the management of high blood pressure in patients in the acute phase of ischemic stroke. We also comment some topics of ischemic stroke treatment. METHODS: A case report of a patient admitted 8 hours after onset of ischemic stroke and with blood pressure of 186x110 mmHg was presented to 120 surgeons and clinician. They were asked to decide the best therapeutic option: to increase, decrease or maintenance blood pressure. RESULTS: Thirty-eight physicians (31,7% considered decreasing blood pressure the best therapeutics, 82 (68,3% considered maintenance and none decided to increase it (p < 0.05. There was no difference between the two specialties conduct. The physicians, with more than 10 years of graduation, had a tendency to decrease the blood pressure (p <0.05. CONCLUSION: The maintenance of blood pressure may present a sufficient blood support to compensate brain flow. A high percentage of the physicians (31,7% do not know about the current concepts of therapeutics considering hypertension in acute ischemic stroke. The development on special units to treat these patients ("stroke units" may eventually

  13. Prevention Of Stroke

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    Nagaraja D

    2005-01-01

    Full Text Available Stroke is an important cause for neurological morbidity and mortality. Prevention of ischemic stroke involves identification and prevention of risk factors and optimal use of pharmacotherapy. Risk factors have been classified as modifiable and non-modifiable; control of modifiable factors should prevent stroke occurrence. Stroke prevention has been described at three levels: primary, secondary and tertiary. Prolonged hypertension increases an individual′s risk for developing fatal or nonfatal stroke by three times and its control has been shown to prevent stroke. Diabetes mellitus is an important cause for microangiopathy and predisposes to stroke. Statin trials have shown significant reduction in stroke in those who were treated with statins. Stroke risk can be reduced by avoiding tobacco use, control of obesity and avoiding sedentary life style. Anti platelet medications are effective for secondary prevention of stroke. Educating society regarding modifiable risk factors and optimal use of pharmacotherapy form the cornerstone for the prevention of stroke.

  14. Brainstem ischemic stroke without permanent sequelae during the course of spontaneous internal carotid artery dissection – case report

    International Nuclear Information System (INIS)

    Nesteruk, Tomasz; Nesteruk, Marta; Bulik-Pasińska, Marta; Boroszko, Dariusz; Ostrowska, Monika

    2012-01-01

    Internal carotid artery dissection (ICAD) is a frequent cause of a stroke in young patients. Risk factors which can lead to dissection include neck injury and diseases of the inner wall of the artery. Common symptoms in ICAD are cervical pain and headache, Horner’s syndrome, paralysis of the cranial nerves and subsequently cerebral and retinal ischemia. MR angiography in TOF technique and brain MRI in T1- and T2-weighted images, FLAIR and DWI sequences are the method of choice in patients with ICAD but contrast-enhanced multislice computed tomography remains the fastest and the most available diagnostic method. A 39-year old woman, previously healthy, presented to the Hospital Emergency Department because of increasing neck pain on the right side and difficulty in swallowing. The neurological examination revealed: drooping of the right eyelid with narrow palpebral fissure, dysarthria, anisocoria (narrower pupil on the right side), unilateral hypoesthesia on the left side, weak palatal and pharyngeal reflexes on both sides, paresthesia within the left half of the body. Seven days before, the patient felt a sudden, severe neck pain radiating to the temporal apophysis. CT angiography revealed a defect in contrast filling within the left internal carotid artery and right vertebral artery. MRI of the head with MR angiography showed internal carotid artery dissection on the left side and dissection of the right vertebral artery and no ischemic changes within the brain. CT and MR angiography are methods characterized by high sensitivity in detecting dissection of the cervical arteries

  15. Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention.

    Science.gov (United States)

    Jeanne, Marion; Jorgensen, Jeff; Gould, Douglas B

    2015-05-05

    Collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form heterotrimers critical for vascular basement membrane stability and function. Patients with COL4A1 or COL4A2 mutations suffer from diverse cerebrovascular diseases, including cerebral microbleeds, porencephaly, and fatal intracerebral hemorrhage (ICH). However, the pathogenic mechanisms remain unknown, and there is a lack of effective treatment. Using Col4a1 and Col4a2 mutant mouse models, we investigated the genetic complexity and cellular mechanisms underlying the disease. We found that Col4a1 mutations cause abnormal vascular development, which triggers small-vessel disease, recurrent hemorrhagic strokes, and age-related macroangiopathy. We showed that allelic heterogeneity, genetic context, and environmental factors such as intense exercise or anticoagulant medication modulated disease severity and contributed to phenotypic heterogeneity. We found that intracellular accumulation of mutant collagen in vascular endothelial cells and pericytes was a key triggering factor of ICH. Finally, we showed that treatment of mutant mice with a US Food and Drug Administration-approved chemical chaperone resulted in a decreased collagen intracellular accumulation and a significant reduction in ICH severity. Our data are the first to show therapeutic prevention in vivo of ICH resulting from Col4a1 mutation and imply that a mechanism-based therapy promoting protein folding might also prevent ICH in patients with COL4A1 and COL4A2 mutations. © 2015 American Heart Association, Inc.

  16. Recurrent spontaneous intracerebral hemorrhage associated with ...

    African Journals Online (AJOL)

    Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is a relatively uncommon form of stroke-it causes only 10 to 15 percent of all strokes. It is more disabling and has a higher mortality rate than ischemic stroke, ...

  17. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity.

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    Gustavo S Masson

    Full Text Available Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR. Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training and sedentary (S SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC, NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR, p38 MAPK and ERK1/2 expression (Western blotting, NF-κB content (electrophoretic mobility shift assay and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control showed increased mean arterial pressure (172±3 mmHg, pressure variability and heart rate (358±7 b/min, decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S. These responses were followed by increased vagal component of heart rate variability (1.9-fold and resting bradycardia (-13% at the 4th week, and, by reduced vasomotor component of pressure variability (-28% and decreased mean arterial pressure (-7% only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro

  18. Aortic depressor nerve stimulation does not impede the dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats.

    Science.gov (United States)

    Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

    2017-05-01

    Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY; n = 8) rats and spontaneously hypertensive rats (SHR; n = 7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, and 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4 ± 14.0 vs. 51.6 ± 11.3 arbitrary units in WKY, P = 0.012; and 248.7 ± 33.9 vs. 181.1 ± 16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8 ± 6.6 vs. 81.2 ± 5.4 mmHg in WKY, P = 0.004; and 128.6 ± 9.8 vs. 114.7 ± 10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55 ± 0.93 vs. 13.03 ± 1.28 dB/decade in WKY, P = 0.542; and 17.37 ± 1.01 vs. 17.47 ± 1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex. Copyright © 2017 the American Physiological Society.

  19. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity.

    Science.gov (United States)

    Masson, Gustavo S; Costa, Tassia S R; Yshii, Lidia; Fernandes, Denise C; Soares, Pedro Paulo Silva; Laurindo, Francisco R; Scavone, Cristoforo; Michelini, Lisete C

    2014-01-01

    Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-κB content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172±3 mmHg), pressure variability and heart rate (358±7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (-13%) at the 4th week, and, by reduced vasomotor component of pressure variability (-28%) and decreased mean arterial pressure (-7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro

  20. Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

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    Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

    2016-03-01

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men.

    Science.gov (United States)

    Dalmasso, Carolina; Patil, Chetan N; Yanes Cardozo, Licy L; Romero, Damian G; Maranon, Rodrigo O

    2017-10-17

    The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  2. What is the optimal duration of middle-cerebral artery occlusion consistently resulting in isolated cortical selective neuronal loss in the spontaneously hypertensive rat?

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    Sohail eEjaz

    2015-03-01

    Full Text Available Introduction and Objectives: Selective neuronal loss (SNL in the reperfused penumbra may impact clinical recovery and is thus important to investigate. Brief proximal middle cerebral artery occlusion (MCAo results in predominantly striatal SNL, yet cortical damage is more relevant given its behavioral implications and that thrombolytic therapy mainly rescues the cortex. Distal temporary MCAo (tMCAo does target the cortex, but the optimal occlusion duration that results in isolated SNL has not been determined. In the present study we assessed different distal tMCAo durations looking for consistently pure SNL.Methods: Microclip distal tMCAo (md-tMCAo was performed in ~6-month old male spontaneously hypertensive rats (SHRs. We previously reported that 45min md-tMCAo in SHRs results in pan-necrosis in the majority of subjects. Accordingly, three shorter MCAo durations were investigated here in decremental succession, namely 30, 22 and 15mins (n=3, 3 and 7 subjects, respectively. Recanalization was confirmed by MR angiography just prior to brain collection at 28 days and T2-weighted MRI was obtained for characterization of ischemic lesions. NeuN, OX42 and GFAP immunohistochemistry appraised changes in neurons, microglia and astrocytes, respectively. Ischemic lesions were categorized into three main types: 1 pan-necrosis; 2 partial infarction; and 3 SNL. Results: Pan-necrosis or partial infarction was present in all 30min and 22min subjects, but not in the 15min group (p < 0.001, in which isolated cortical SNL was consistently present. MRI revealed characteristic hyperintense abnormalities in all rats with pan-necrosis or partial infarction, but no change in any 15min subject. Conclusions: We found that 15min distal MCAo consistently resulted in pure cortical SNL, whereas durations equal or longer than 22min consistently resulted in infarcts. This model may be of use to study the pathophysiology of cortical SNL and its prevention by appropriate

  3. Comparison of the validity of the use of the spontaneously hypertensive rat as a model of attention deficit hyperactivity disorder in males and females.

    Science.gov (United States)

    Bayless, Daniel W; Perez, Maria C; Daniel, Jill M

    2015-06-01

    The spontaneously hypertensive rat (SHR) is a commonly used and well-studied rodent model of attention deficit hyperactivity disorder (ADHD). Sex differences in the cognitive symptoms of ADHD are reported. However, the female SHR rat is much less studied than its male counterpart. The goal of the current study was to assess the validity of the SHR rodent model of ADHD by examining attentional performance, inhibitory control, and hyperactivity in both male and female SHR rats. Adult SHR and control Wistar-Kyoto rats were trained on the 5-choice serial reaction time task, a self-paced test of attention and inhibitory control. This task requires animals to identify the location of a brief light stimulus among five possible locations under several challenging conditions. Analyses of percent correct revealed that attentional performance in SHR females was not significantly different from control females, whereas attentional performance in SHR males was significantly different from control males. Analyses of the number of premature responses revealed that SHR rats made more inhibitory control errors than did control rats and that this decrease in inhibitory control was present in both SHR males and females. Analyses of activity in the open field revealed that SHR rats were more hyperactive than were control rats and that this increased hyperactivity was present in both SHR males and females. The current findings have implications for the study of sex differences in ADHD and for the use of SHR rats as a model of ADHD in females. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Transcriptome of the NTS in exercise-trained spontaneously hypertensive rats: implications for NTS function and plasticity in regulating blood pressure.

    Science.gov (United States)

    Waki, Hidefumi; Gouraud, Sabine S; Bhuiyan, Mohammad E R; Takagishi, Miwa; Yamazaki, Toshiya; Kohsaka, Akira; Maeda, Masanobu

    2013-01-07

    The nucleus tractus solitarii (NTS) controls the cardiovascular system during exercise, and alteration of its function may underlie exercise-induced cardiovascular adaptation. To understand the molecular basis of the NTS's plasticity in regulating blood pressure (BP) and its potential contribution to the antihypertensive effects, we characterized the gene expression profiles at the level of the NTS after long-term daily wheel running in spontaneously hypertensive rats (SHRs). Genome-wide microarray analysis was performed to screen for differentially expressed genes in the NTS between exercise-trained (12 wk) and control SHRs. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that daily exercise altered the expression levels of NTS genes that are functionally associated with metabolic pathways (5 genes), neuroactive ligand-receptor interactions (4 genes), cell adhesion molecules (3 genes), and cytokine-cytokine receptor interactions (3 genes). One of the genes that belonged to the neuroactive ligand-receptor interactions category was histamine receptor H(1). Since we confirmed that the pressor response induced by activation of this receptor is increased after long-term daily exercise, it is suggested that functional plasticity in the histaminergic system may mediate the facilitation of blood pressure control in response to exercise but may not be involved in the lowered basal BP level found in exercise-trained SHRs. Since abnormal inflammatory states in the NTS are known to be prohypertensive in SHRs, altered gene expression of the inflammatory molecules identified in this study may be related to the antihypertensive effects in exercise-trained SHRs, although such speculation awaits functional validation.

  5. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

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    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

  6. Chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in adult spontaneously hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Pires, Vanessa A; Pamplona, Fabrício A; Pandolfo, Pablo; Prediger, Rui D S; Takahashi, Reinaldo N

    2010-12-20

    The spontaneously hypertensive rat (SHR) is frequently used as an experimental model for the study of attention deficit hyperactivity disorder (ADHD) since it displays behavioural and neurochemical features of ADHD. Increasing evidence suggests that caffeine might represent an important therapeutic tool for the treatment of ADHD and we recently demonstrated that the acute administration of caffeine improves several learning and memory impairments in adult SHR rats. Here we further evaluated the potential of caffeine in ADHD therapy. Female Wistar (WIS) and SHR rats were treated with caffeine (3mg/kg, i.p.) or methylphenidate (MPD, 2mg/kg, i.p.) for 14 consecutive days during the prepubertal period (post-natal days 25-38) and they were tested later in adulthood in the object-recognition task. WIS rats discriminated all the objects used, whereas SHR were not able to discriminate pairs of objects with subtle structural differences. Chronic treatment with caffeine or MPD improved the object-recognition deficits in SHR rats. Surprisingly, these treatments impaired the short-term object-recognition ability in adult WIS rats. The present drug effects are independent of changes in locomotor activity, arterial blood pressure and body weight in both rat strains. These findings suggest that chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in discriminative learning impairments of SHR, suggesting caffeine as an alternative therapeutic strategy for the early management of ADHD symptoms. Nevertheless, our results also emphasize the importance of a correct diagnosis and the caution in the use of stimulant drugs such as caffeine and MPD during neurodevelopment since they can disrupt discriminative learning in non-ADHD phenotypes. Copyright 2010 Elsevier B.V. All rights reserved.

  7. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

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    Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  8. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sung, Jin Young; Choi, Hyoung Chul

    2011-01-01

    Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  9. Análisis ecocardiográfico de la geometría ventricular izquierda en ratas espontáneamente hipertensas Echocardiographic study of left ventricular geometry the in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Eduardo M. Escudero

    2009-06-01

    Full Text Available El presente trabajo fue diseñado para analizar ecocardiográficamente la geometría del ventrículo izquierdo en ratas espontáneamente hipertensas (SHR. Se estudiaron 114 ratas macho de 4 meses de edad, 73 SHR y 41 Wistar (W a las que se les registró la presión arterial, la frecuencia cardíaca y se les realizó un ecocardiograma. Con las mediciones de diámetros y espesores de la pared ventricular izquierda se calcularon el espesor parietal relativo (h/r, el índice de masa del ventrículo izquierdo (IMVI, el volumen minuto, y el acortamiento medio ventricular. La geometría ventricular izquierda normal fue definida analizando el grupo de ratas normotensas y fijando los límites de IMVI y h/r a partir de la media más 2 desvíos estándar. Los patrones de geometría anormal se definieron como: remodelado concéntrico (RC: IMVI 0.71; hipertrofia excéntrica (HE: IMVI>2.06 mg/g - h/r 2.06 mg/g - h/r > 0.71. La presión arterial sistólica y el volumen minuto se utilizaron para estimar la resistencia periférica total (RPT. Doce por ciento de SHR presentaron geometría ventricular izquierda normal; 18% RC; 33% HC y 37% HE. El RC mostró el volumen latido más pequeño y la RPT más alta de cualquier grupo. HE presentó presión arterial sistólica similar a la de los otros grupos de SHR, volumen latido más alto y la RPT más baja. Estos hallazgos en SHR exhibiendo diferentes patrones de geometría ventricular izquierda, similares a los referidos en humanos, intensifican las similitudes entre la hipertensión esencial humana y las SHR.The purpose of this study was to analyze by echocardiogram left ventricular (LV geometry in spontaneously hypertensive rats (SHR. Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W. Left ventricular mass index (LVMI, relative wall thickness (RWT, stroke volume, and mid ventricular shortening were calculated with echocardiographic

  10. Thromboembolic events with recombinant activated factor VII in spontaneous intracerebral hemorrhage: results from the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial.

    Science.gov (United States)

    Diringer, Michael N; Skolnick, Brett E; Mayer, Stephan A; Steiner, Thorsten; Davis, Stephen M; Brun, Nikolai C; Broderick, Joseph P

    2010-01-01

    Patients with intracerebral hemorrhage have a high risk of thromboembolic events (TEs) due to advanced age, hypertension, atherosclerosis, diabetes, and immobility. Use of recombinant activated factor VII (rFVIIa) could increase TEs in high-risk patients. Factor Seven for Acute Hemorrhagic Stroke (FAST) trial data were reviewed to define the frequency of and risk factors for TE with rFVIIa. Eight hundred forty-one patients presenting hemorrhage were randomized to 20 or 80 microg/kg of rFVIIa or placebo. Those with Glasgow Coma Scale score surgery, coagulopathy, or recent TE were excluded. Myocardial, cerebral, or venous TEs were subject to detailed reporting and expedited local review. Additionally, a blinded Data Monitoring Committee reviewed all electrocardiograms, centrally analyzed troponin I values, and CT scans. There were 178 arterial and 47 venous TEs. Venous events were similar across groups. There were 49 (27%) arterial events in the placebo group, 47 (26%) in the 20-microg/kg group, and 82 (46%) in the 80 microg/kg group (P=0.04). Of the myocardial events, 38 were investigator-reported and 103 identified by the Data Monitoring Committee. They occurred in 17 (6.3%) placebo and 57 (9.9%) rFVIIa patients (P=0.09). Arterial TEs were associated with: receiving 80 microg/kg rFVIIa (OR=2.14; P=0.031), signs of cardiac or cerebral ischemia at presentation (OR=4.19; P=0.010), age (OR=1.14/5 years; P=0.0123), and prior use of antiplatelet agents (OR=1.83; P=0.035). Ischemic strokes possibly related to study drug occurred in 7, 5, and 8 patients in the placebo, 20 microg/kg, and 80-microg/kg groups, respectively. Higher doses of rFVIIa in a high-risk population are associated with a small increased risk of what are usually minor cardiac events. Demonstration of the ability of rFVIIa to improve outcome in future studies should be driven by its effectiveness in slowing bleeding outweighting the risk of a small increase in arterial TEs.

  11. Clinical features of multiple spontaneous intracerebral hemorrhages

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    Tao CHANG

    2016-01-01

    Full Text Available Objective To analyze the clinical features of multiple spontaneous intracerebral hemorrhages (MICH. Methods Conservative therapy, puncture and drainage, hematoma removal and/or decompressive craniectomy were used in the treatment of 630 intracerebral hemorrhage (ICH patients, who were divided into 2 groups: 30 cases with MICH and another 600 cases with solitary intracerebral hemorrhage (SICH. Three months after onset, modified Rankin Scale (mRS was used to evaluate the prognosis of all cases. Results Compared with patients in SICH group, the occurrence rate of hypertension > 5 years (P = 0.008, diabetes mellitus (P = 0.024, hypercholesterolemia (P = 0.050 and previous ischemic stroke (P = 0.026 were all significantly higher in MICH group. The mean arterial pressure (MAP level (P = 0.002 and the incidence of limb movement disorder (P = 0.000 were significantly higher in patients with MICH than those with SICH. Basal ganglia and thalamus were the predilection sites of hematoma (P = 0.001. Patients with MICH had worse prognosis compared to those with SICH 3 months after onset (P = 0.006. Conclusions Hypertension > 5 years, diabetes mellitus, hypercholesterolemia and ischemic stroke were identified to be the pathophysiological basis of MICH in this study. All patients with MICH had more serious clinical manifestations after onset and worse prognosis. DOI: 10.3969/j.issn.1672-6731.2016.01.008

  12. A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY

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    Gullberg, Grant, T; Huesman, Ronald, H; Reutter, Bryan, W; Sitek, Arkadiusz; Veress, Alexander, I; Weiss, Jeffrey, A; Yang, Yongfeng

    2017-06-13

    Problem: In the case of hypertrophy caused by pressure overload (hypertension) there is an increase in cardiac mass and modification cardiac metabolism. Aim: This study was designed to study the changes in glucose metabolism, ejection fraction, and deformation in the left ventricle with the progression of hypertrophy in spontaneous hypertensive rats (SHR). Methods: Dynamic PET data were acquired using the microPET II at UC Davis. Two rats were imaged at 10-week intervals for 18 months. Each time a dose of approximately 1- 1.5 mCi of F-18-FDG was injected into a normotensive Wistar Kyoto (WKY) rat and the same dose was injected into a SHR rat. Each rat was imaged using a gated dynamic acquisition for 80 minutes acquiring list mode data with cardiac gating of approximately 600-900 million total counts. For the analysis of glucose of metabolism, the list mode data were histogrammed into a dynamic sequence (42 frames over 80 mins). For each time frame, projection data of 1203 140x210 sinograms of 0.582 mm bins were formed by summing the last three gates before and one after the R-wave trigger to correspond to the diastolic phase of the cardiac cycle. Dynamic sequences of 128x128x83 matrices of 0.4x0.4x0.582 mm3 voxels in x, y, and z were reconstructed using an iterative MAP reconstruction which used a prior that penalized the high frequency components of the reconstruction using appropriate weighting between 26 nearest neighboring voxels. Time activity curves were generated from the dynamic reconstructed sequence for the blood and left ventricular tissue regions of interest which were fit to a 2-compartment model to obtain a least squares fit for the kinetic parameters. For the analysis of deformation, the list mode data were histogrammed into 8 gates of the cardiac cycle, each gate was the total sum of the later 60 mins of the 80 min acquisition. Images of 128x128x83 matrices for each gate were reconstructed using the same iterative MAP reconstruction used to

  13. The ThRombolysis in UnconTrolled Hypertension (TRUTH) protocol: an observational study on treatment strategy of elevated blood pressure in stroke patients eligible for IVT.

    Science.gov (United States)

    Zonneveld, T P; Algra, A; Dippel, D W J; Kappelle, L J; van Oostenbrugge, R J; Roos, Y B W E M; Wermer, M J; van der Worp, H B; Nederkoorn, P J; Kruyt, N D

    2015-11-23

    Intravenous thrombolysis (IVT) with (recombinant) tissue plasminogen activator is an effective treatment in acute ischemic stroke. However, IVT is contraindicated when blood pressure is above 185/110 mmHg, because of an increased risk on symptomatic intracranial hemorrhage. In current Dutch clinical practice, two distinct strategies are used in this situation. The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT. In the conservative strategy, IVT is administered only when blood pressure drops spontaneously below protocolled thresholds. A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group; robust evidence for either strategy, however, is lacking. We hypothesize that (I) the active strategy leads to a better functional outcome three months after acute ischemic stroke. Secondary hypotheses are that this effect occurs despite (II) increasing the number of symptomatic intracranial hemorrhages, and could be attributable to (III) a higher rate of IVT treatments and (IV) a shorter door-to-needle time. The TRUTH is a prospective, observational, cluster-based, parallel group follow-up study; in which participating centers continue their current local treatment guidelines. Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy. The primary outcome is functional outcome on the modified Rankin Scale at three months. Secondary outcomes are symptomatic intracranial hemorrhage, IVT treatment and door-to-needle time. We based our sample size estimate on an ordinal analysis of the mRS with the "proportional odds" model. With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05, this analysis would have an 80 % power with a total number of 600 patients

  14. Combined treatment with a β3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Suzuki, Toshiro; Saito, Tetsuichi; Yokoyama, Hitoshi; Nakazawa, Masaki; Ishizuka, Osamu

    2017-04-01

    This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the β 3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the β 3 -ARs and M 3 -MRs expressed within the urinary bladders were analyzed. Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M 3 -MR and β 3 -AR mRNA. The tissue distribution of M 3 -MRs was similar to that of the β 3 -ARs. This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

  15. Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

    Science.gov (United States)

    2014-01-01

    Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a behavioral disorder affecting 3-5% of children. Although ADHD is highly heritable, environmental factors like exposure during early development to various toxic substances like polychlorinated biphenyls (PCBs) may contribute to the prevalence. PCBs are a group of chemical industrial compounds with adverse effects on neurobiological and cognitive functioning, and may produce behavioral impairments that share significant similarities with ADHD. The present study examined the relation between exposure to PCB 153 and changes in ADHD-like behavior in an animal model of ADHD, the spontaneously hypertensive rats (SHR/NCrl), and in Wistar Kyoto (WKY/NHsd) controls. Methods SHR/NCrl and WKY/NHsd, males and females, were orally given PCB 153 dissolved in corn oil at around postnatal day (PND) 8, 14, and 20 at a dosage of 1, 3 or 6 mg/kg bodyweight at each exposure. The control groups were orally administered corn oil only. The animals were behaviorally tested for exposure effects from PND 37 to 64 using an operant procedure. Results Exposure to PCB 153 was associated with pronounced and long-lasting behavioral changes in SHR/NCrl. Exposure effects in the SHR/NCrl depended on dose, where 1 mg/kg tended to reduce ADHD-like behaviors and produce opposite behavioral effects compared to 3 mg/kg and 6 mg/kg, especially in the females. In the WKY/NHsd controls and for the three doses tested, PCB 153 exposure produced a few specific behavioral changes only in males. The data suggest that PCB 153 exposure interacts with strain and sex, and also indicate a non-linear dose–response relation for the behaviors observed. Conclusions Exposure to PCB 153 seems to interact with several variables including strain, sex, dose, and time of testing. To the extent that the present findings can be generalized to humans, exposure effects of PCB 153 on ADHD behavior depends on amount of exposure, where high doses may aggravate ADHD

  16. Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Baskin, Britahny M; Dwoskin, Linda P; Kantak, Kathleen M

    2015-04-01

    Past research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder showed that adolescent methylphenidate treatment enhanced cocaine abuse risk in SHR during adulthood. The acquisition of cocaine self-administration was faster, and cocaine dose-response functions were shifted upward under fixed-ratio and progressive ratio schedules compared to adult SHR that received adolescent vehicle treatment or to control strains that received adolescent methylphenidate treatment. The current study determined if extending treatment beyond adolescence would ameliorate long-term consequences of adolescent methylphenidate treatment on cocaine abuse risk in adult SHR. Treatments (vehicle or 1.5mg/kg/day oral methylphenidate) began on postnatal day 28. Groups of male SHR were treated with vehicle during adolescence and adulthood, with methylphenidate during adolescence and vehicle during adulthood, or with methylphenidate during adolescence and adulthood. The group receiving adolescent-only methylphenidate was switched to vehicle on P56. Cocaine self-administration began on postnatal day 77, and groups receiving methylphenidate during adolescence and adulthood were treated either 1-h before or 1-h after daily sessions. At baseline under a fixed-ratio 1 schedule, cocaine self-administration (2h sessions; 0.3mg/kg unit dose) did not differ among the four treatment groups. Under a progressive ratio schedule (4.5h maximum session length; 0.01-1.0mg/kg unit doses), breakpoints for self-administered cocaine in SHR receiving the adult methylphenidate treatment 1-h pre-session were not different from the vehicle control group. However, compared to the vehicle control group, breakpoints for self-administered cocaine at the 0.3 and 1.0mg/kg unit doses were greater in adult SHR that received adolescent-only methylphenidate or received methylphenidate that was continued into adulthood and administered 1-h post-session. These findings suggest that

  17. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China (China); Chonan, Ritsu [Koei Kogyo Co., Ltd., Tokyo, 101-0063 Japan (Japan); Yamahara, Johji [Pharmafood Institute, Kyoto, 602-8136 Japan (Japan); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 China (China); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000 Australia (Australia)

    2014-10-15

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  18. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    International Nuclear Information System (INIS)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-01-01

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  19. Amlodipine and atorvastatin improved hypertensive cardiac hypertrophy through regulation of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin system in spontaneous hypertension rats.

    Science.gov (United States)

    Lu, Jingchao; Liu, Fan; Liu, Demin; Du, Hong; Hao, Jie; Yang, Xiuchun; Cui, Wei

    2016-06-01

    The present study aims to study the role of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin (RANKL/RANK/OPG) system in cardiac hypertrophy in a spontaneous hypertension rat (SHR) model and the effects of amlodipine and atorvastatin intervention. Thirty-six-week-old male SHRs were randomly divided into four groups: 1) SHR control group; 2) amlodipine alone (10 mg/kg/d) group, 3) atorvastatin alone (10 mg/kg/d) group, 4) combination of amlodinpine and atorvastatin (10 mg/kg/d for each) group. Same gender, weight, and age of Wistar-Kyoto (WKY) rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The thicknesses of left ventricle walls, left ventricle weight, and cardiac function were measured by transthoracic echocardiography. Left ventricular pressure and function were assessed by hemodynamic examination. Cardiomyocyte hypertrophy and collagen accumulation in cardiac tissue were measured by hematoxylin and eosin (HE) and Masson staining, respectively. The hydroxyproline content of cardiac tissue was examined by biochemistry technique. RANKL, RANK and OPG mRNA, protein expression and tissue localization were studied by RT-PCR, Immunohistochemistry and Western blot. Treatment with amlodipine or atorvastatin alone significantly decreased left ventricular mass index, cardiomyocyte cross-sectional area and interstitial fibrosis in SHR (each P < 0.05). Moreover, combined amlodipine and atorvastatin treatment induced significant reversal of left ventricular hypertrophy and decreased cardiomyocyte cross-sectional area and interstitial fibrosis in SHR to a greater extent than each agent alone (P < 0.05). Compared with WKY rats, the myocardial expression of RANKL, RANK, and OPG was increased. Both amlodipine and atorvastatin reduced RANKL, RANK, and OPG expression, with the best effects seen with the combination. Based on our results

  20. Effects of captopril treatment on augmented norepinephrine-stimulated calcium entry through voltage-dependent calcium channels in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Paulis, Ĺudovít; Dobešová, Zdenka; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S4 (2006), S338-S338 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] R&D Projects: GA MZd(CZ) NR7786 Keywords : voltage-dependent calcium channel * hypertension * captopril * norepinephrine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  1. [Hypertension in the elderly].

    Science.gov (United States)

    Handschin, Anja; Henny-Fullin, Katja; Buess, Daniel; Leuppi, Jörg; Dieterle, Thomas

    2015-06-01

    Arterial hypertension remains the most important risk factor for cardiovascular and renal diseases. In view of an increasing prevalence with older age and an increasingly aging population, the treatment of elderly patients with arterial hypertension will become increasingly important in daily practice. Arterial hypertension in the elderly differs in many aspects from arterial hypertension in younger patients. For example, isolated systolic hypertension is the predominant form of arterial hypertension in the elderly. In comparison to younger patients, treatment of hypertension in the elderly is less well investigated. However, available data suggest that lowering of blood pressure in the elderly and very elderly reduces the risk of heart failure, stroke, and even mortality. The best evidence for the treatment of hypertension in the elderly exists for diuretics and calcium antagonists. However, the primary choice of ant