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

Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

DEFF Research Database (Denmark)

Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning

2006-01-01

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adre...

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......, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences......, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end...

Effects of spontaneously hypertensive rat plasma on blood pressure and tail artery calcium uptake in normotensive rats

International Nuclear Information System (INIS)

Lewanczuk, R.Z.; Wang, J.; Zhang, Z.R.; Pang, P.K.

1989-01-01

Previous studies have described the presence of humoral hypertensive factors in spontaneously hypertensive rats (SHR). Other studies have described factors that increase calcium uptake in vascular tissue. In this study, we attempted to confirm, and thereby correlate, the presence of both types of factors in SHR plasma. Intravenous infusion or bolus administration of dialyzed SHR plasma consistently induced an increase in blood pressure in normotensive rats. This hypertensive response was somewhat delayed, with peak blood pressures occurring 45 minutes after bolus administration and 90 minutes after infusion of SHR plasma. Spontaneously hypertensive rat plasma also increased 45 Ca uptake in isolated normotensive rat tail arteries in a dose-dependent manner, with a time course similar to that for the hypertensive response to bolus administration. These findings suggest, therefore, that a substance exists in SHR plasma that can increase intracellular calcium in vascular tissues and thereby increase blood pressure

Transcriptional alterations in the left ventricle of three hypertensive rat models.

Science.gov (United States)

Cerutti, Catherine; Kurdi, Mazen; Bricca, Giampiero; Hodroj, Wassim; Paultre, Christian; Randon, Jacques; Gustin, Marie-Paule

2006-11-27

Left ventricular hypertrophy (LVH) is commonly associated with hypertension and represents an independent cardiovascular risk factor. The aim of this study was to test the hypothesis that the cardiac overload related to hypertension is associated to a specific gene expression pattern independently of genetic background. Gene expression levels were obtained with microarrays for 15,866 transcripts from RNA of left ventricles from 12-wk-old rats of three hypertensive models [spontaneously hypertensive rat (SHR), Lyon hypertensive rat (LH), and heterozygous TGR(mRen2)27 rat] and their respective controls. More than 60% of the detected transcripts displayed significant changes between the three groups of normotensive rats, showing large interstrain variability. Expression data were analyzed with respect to hypertension, LVH, and chromosomal distribution. Only four genes had significantly modified expression in the three hypertensive models among which a single gene, coding for sialyltransferase 7A, was consistently overexpressed. Correlation analysis between expression data and left ventricular mass index (LVMI) over all rats identified a larger set of genes whose expression was continuously related with LVMI, including known genes associated with cardiac remodeling. Positioning the detected transcripts along the chromosomes pointed out high-density regions mostly located within blood pressure and cardiac mass quantitative trait loci. Although our study could not detect a unique reprogramming of cardiac cells involving specific genes at early stage of LVH, it allowed the identification of some genes associated with LVH regardless of genetic background. This study thus provides a set of potentially important genes contained within restricted chromosomal regions involved in cardiovascular diseases.

Hypertension after bilateral kidney irradiation in young and adult rats

International Nuclear Information System (INIS)

Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

1987-01-01

The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension

Water and exchangeable sodium in Goldblatt two-kidney, two-clip hypertensive rats

International Nuclear Information System (INIS)

Mac Cormack, W.P.; Roson, M.I.; Maquieira, M.K.; Mendez, M.A.; Santoro, F.M.; Morera, S.; de la Riva, I.J.

1986-01-01

Exchangeable 22 Na (ExNa), total body water (TBW) and the inulin space (InSp) were determined in two-kidney, two-clip (2K-2C) hypertensive and sham operated (normotensive) control rats 6-8 weeks after surgery. TBW (ml/kg lean body weight) was the same in hypertensive and sham rats. In contrast, ExNa (mEq/kglbw) and InSp (ml/kglbw) significantly increased (p less than 0.01) in rats whose hypertension did not exceed 170 mmHg. Consequently, sham, moderate hypertensive (less than 170 mmHg) and severe hypertensive (less than 170 mmHg) animals showed equal TBW but differed in body water distribution in that moderately hypertensive animals displayed a redistribution of water in favor of the extracellular space

Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

1988-01-01

Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

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Seok Choi

2014-12-01

Conclusion: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

Age-dependent salt hypertension in Dahl rats: fifty years of research.

Science.gov (United States)

Zicha, J; Dobešová, Z; Vokurková, M; Rauchová, H; Hojná, S; Kadlecová, M; Behuliak, M; Vaněčková, I; Kuneš, J

2012-01-01

Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension - salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of renin-angiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the salt-sensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake. On the contrary, moderate salt hypertension in adult Dahl rats is

Anti-hypertensive effect of Gastrodia elata Bl leaf extract in rats

African Journals Online (AJOL)

Methods: The two-kidney one-clip (2K1C) Goldblatt model of renovascular hypertension was used in. Wistar rats. ... urea levels of the rats were measured by enzyme-linked immunosorbent assay (ELISA). Superoxide ... Hypertension is the most common risk factor for .... (BP-6 noninvasive Electro-Sphygmomanometer,.

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

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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.

Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.

Science.gov (United States)

Han, Su Young; Bouwer, Gregory T; Seymour, Alexander J; Korpal, Aaron K; Schwenke, Daryl O; Brown, Colin H

2015-11-01

Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Norepinephrine accumulation by the rat caudal artery in the presence of hypertensive plasma

International Nuclear Information System (INIS)

Freas, W.; Thompson, D.A.; Hart, J.L.; Muldoon, S.M.

1986-01-01

We have partially isolated endogenous factors from canine plasma which inhibit 3 H-norepinephrine (NE) accumulation by the canine saphenous vein. The purpose of this study is to determine if these circulating factors may account for the observed differences in 3 H-NE uptake by hypertensive and normotensive blood vessels. Three models of hypertension were examined in this study. Blood vessels were compared from SHR and WKY rats, deoxycorticosterone acetate (DOCA) and control rats, and reduced renal mass (RRM) and control rats. There was no significant difference in 3 H-NE accumulation between blood vessels obtained from RRM and paired control rats. However, both the SHR and DOCA hypertensive caudal arteries and aorta accumulated significantly more 3 H-NE than their corresponding control tissues. There was not a significant change in 3 H-NE accumulation between hypertensive and control vena cava and mesenteric arteries. Normotensive and hypertensive plasma inhibited 3 H-NE accumulation by the rat caudal artery. However, there was not a correlation between blood pressure of plasma donor rats and accumulation of 3 H-NE. Therefore, although there are differences in 3 H-NE accumulation between hypertensive and normotensive blood vessels, plasma does not contain a factor responsible for this observed difference

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

Science.gov (United States)

Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2013-11-01

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

Cyclophilin B expression in renal proximal tubules of hypertensive rats.

Science.gov (United States)

Kainer, D B; Doris, P A

2000-04-01

Rat cyclophilin-like protein (Cy-LP) is a candidate hypertension gene initially identified by differential hybridization and implicated in renal mechanisms of salt retention and high blood pressure. We report the molecular characterization of rat cyclophilin B (CypB) and demonstrate, through sequence analysis and an allele-specific polymerase chain reaction primer assay, that CypB but not Cy-LP is expressed in rat kidney. CypB is an endoplasmic reticulum-localized prolyl-isomerase that interacts with elongation initiation factor 2-beta, an important regulator of protein translation and a central component of the endoplasmic reticulum stress response to hypoxia or ATP depletion. Active renal transport of sodium is increased in the spontaneously hypertensive rat (SHR), and there is evidence that this coincides with hypoxia and ATP depletion in the renal cortex. In the present studies we have examined expression of CypB in rat proximal tubules, which contributes to the increased renal sodium reabsorption in this model of hypertension. We report that CypB transcript abundance is significantly elevated in proximal convoluted tubules from SHR compared with the control Wistar-Kyoto strain. This upregulation occurs in weanling animals and precedes the development of hypertension, indicating that it is not a simple response to hypertension in SHR. Further, CypB expression is also higher in a proximal tubule cell line derived from SHR compared with a similar line derived from Wistar-Kyoto rats, indicating that this difference is genetically determined. No sequence differences were observed in the CypB cDNA from these 2 strains. These observations suggest that a genetically determined alteration in proximal tubules from SHR occurs that leads to increased expression of CypB. In view of evidence linking CypB to the regulation of elongation initiation factor-2, the upregulation of CypB may result from metabolic stress.

Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

Science.gov (United States)

Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G

2014-02-01

Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

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

Effect of hypertensive rat plasma on ion transport of cultured vascular smooth muscle

International Nuclear Information System (INIS)

Magargal, W.W.; Overbeck, H.W.

1986-01-01

We layered fresh, unprocessed plasma from healthy rats with early (less than or equal to 7 days) or benign, chronic (greater than 3 wk) one-kidney, one-clip hypertension and from paired one-kidney normotensive control rats over confluent primary-cultured rat aortic smooth muscle cells. Plasma from all rats increased cellular ouabain-sensitive 86 Rb + uptake and sodium content and decreased ouabain-insensitive 86 Rb + uptake compared with uptakes and content in the presence of balanced salt solution (P less than 0.01). Cells incubated in the presence of plasma from rats with early (P less than 0.02) or chronic hypertension (P less than 0.01) had significantly reduced ouabain-sensitive 86 Rb + uptake when compared with cells incubated in normotensive plasma, but their intracellular Na+ contents were not lower. We no longer detected this uptake difference when chronic hypertensives drank 0.9% NaCl instead of water. Plasma from hypertensive rats also altered ouabain-insensitive 86 Rb + uptake by the cultured cells. These findings of this new, reproducible, and specific assay system support the hypothesis that plasma factors inhibit the membrane sodium-potassium pump in vascular smooth muscle cells in this form of hypertension. The abnormality occurs in both early and chronic stages, but may not be related to sodium intake. The data also provide evidence for plasma factors in hypertension altering membrane K+ permeability

Characterization of renal hyperemia in portal hypertensive rats

International Nuclear Information System (INIS)

Premen, A.J.; Banchs, V.; Go, V.L.W.; Benoit, J.N.; Granger, D.N.

1986-01-01

In anesthetized sham-operated control (C) and portal vein stenosed (PVS) rats, renal blood flow (RBF) was measured with radioactive microspheres on days 2, 4, 6, 8, and 10 following surgery. On day 2, only a small increase in RBF (19%) was produced in PVS versus C rats. However, by day 4, a significant increase in RBF (35%) was observed in PVS versus C animals. By day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than in C rats. Thereafter (on days 8 and 10), the renal hyperemia remained at the maximal value. In a separate group of 10-day PVS rats, glucagon antiserum failed to attenuate the 44% increase in RBF observed in PVS versus C rats. Radioimmunoassay of C and PVS plasma (10-day samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin/gastrin, neurotensin, pancreatic polypeptide, beta-endorphin, and peptide histidine-isoleucine amide are not elevated in arterial plasma of PVS rats. These data indicate that the renal hyperemia induced by chronic portal hypertension is manifested within 4 days after the hypertensive insult. Our studies also suggest that at least 9 blood-borne gastrointestinal peptides are not directly involved in the renal response to portal vein stenosis

Characterization of renal hyperemia in portal hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Premen, A.J.; Banchs, V.; Go, V.L.W.; Benoit, J.N.; Granger, D.N.

1986-03-01

In anesthetized sham-operated control (C) and portal vein stenosed (PVS) rats, renal blood flow (RBF) was measured with radioactive microspheres on days 2, 4, 6, 8, and 10 following surgery. On day 2, only a small increase in RBF (19%) was produced in PVS versus C rats. However, by day 4, a significant increase in RBF (35%) was observed in PVS versus C animals. By day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than in C rats. Thereafter (on days 8 and 10), the renal hyperemia remained at the maximal value. In a separate group of 10-day PVS rats, glucagon antiserum failed to attenuate the 44% increase in RBF observed in PVS versus C rats. Radioimmunoassay of C and PVS plasma (10-day samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin/gastrin, neurotensin, pancreatic polypeptide, beta-endorphin, and peptide histidine-isoleucine amide are not elevated in arterial plasma of PVS rats. These data indicate that the renal hyperemia induced by chronic portal hypertension is manifested within 4 days after the hypertensive insult. Our studies also suggest that at least 9 blood-borne gastrointestinal peptides are not directly involved in the renal response to portal vein stenosis.

Long working hours and risk for hypertension in Japanese male white collar workers

OpenAIRE

Nakanishi, N; Yoshida, H; Nagano, K; Kawashimo, H; Nakamura, K; Tatara, K

2001-01-01

STUDY OBJECTIVE—To evaluate the association of long working hours with the risk for hypertension.
DESIGN—A five year prospective cohort study.
SETTING—Work site in Osaka, Japan.
PARTICIPANTS—941 hypertension free Japanese male white collar workers aged 35-54 years were prospectively examined by serial annual health examinations. Men in whom borderline hypertension and hypertension were found during repeated surveys were defined as incidental cases of borderline hypertension and hypertension.
...

BAY 41-2272 Treatment Improves Acetylcholine-Induced Aortic Relaxation in L-NAME Hypertensive Rats.

Science.gov (United States)

Prawez, Shahid; Ahanger, Azad Ahmad; Singh, Thakur Uttam; Mishra, Santosh Kumar; Sarkar, Souvendra Nath; Kumar, Dinesh

2016-12-01

Hypertension, an emerging problem of recent era, and many pathophysiological factors are participating to produce the disease. Nitric oxide (NO) is an important constituent to ameliorate hypertensive condition. Inhibition of endogenous NO synthase by L-N G -Nitroarginine methyl ester (L-NAME) was responsible for generating hypertension in rats. BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine), a soluble guanylyl cyclase activator, restricts rise of blood pressure and shows cardioprotective activity. The aim of the present study was to analyze effect of short-term BAY 41-2272 treatment on blood pressure and vascular function. Male Wistar rats were randomly divided into three groups such as control (group-A), hypertensive (group-B), and BAY 41-2272-treated hypertensive (group-C) rats. Normal saline was administered intramuscularly to control rats for last 3 days (days 40, 41, and 42) of total 42 days treatment, whereas rats of group-B and group-C were treated with L-NAME hydrochloride in drinking water at 50 mg/kg body weight daily for 42 days. Also, normal saline and BAY 41-2272 were administered for last 3 days at two different dosages at 1 and 3 mg/kg body weight/day intramuscularly to group-B and group-C rats, respectively. Administration of BAY 41-2272 for 3 days was not sufficient enough to decrease mean arterial pressure of hypertensive rats significantly. BAY at both the treatment dosages significantly ameliorate acetylcholine-induced maximal aortic relaxation compared with BAY-untreated hypertensive rats. Findings of the present study indicate that even shorter period of BAY 41-2272 treatment (3 days) improves vascular relaxation.

Therapeutic vaccines against human and rat renin in spontaneously hypertensive rats.

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Zhihua Qiu

Full Text Available Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. As the initiation factor of renin-angiotensin system, renin plays a critical role in hypertension. In this study, we selected six peptides (rR32, rR72, rR215, hR32, hR72, and hR215 belonging to potential epitopes of rat and human renin. The main criteria were as follows: (1 include one of renin catalytic sites or the flap sequence; (2 low/no-similarity when matched with the host proteome; (3 ideal antigenicity and hydrophilicity. The peptides were coupled to keyhole limpet hemocyanin and injected into SpragueDawley (SD rats, spontaneously hypertensive rats (SHRs and Wistar-Kyoto rats. The antisera titers and the binding capacity with renin were detected. The effects of the anti-peptides antibodies on plasma renin activity (PRA and blood pressure were also determined. All peptides elicited strong antibody responses. The antisera titers ranged from 1:32,000 to 1:80,000 in SD rats on day 63. All antisera could bind to renin in vitro. Compared with the control antibody, the antibodies against the rR32, hR32, rR72 and hR72 peptides inhibited PRA level by up to about 50%. Complete cross-reactivity of the anti-rR32 antibody and the anti-hR32 antibody was confirmed. The epitopes rR32 and hR32 vaccines significantly decreased systolic blood pressure (SBP of SHRs up to 15mmHg (175±2 vesus 190±3 mmHg, P = 0.035; 180±2 vesus 195±3 mmHg, P = 0.039, while no obvious effect on SD rats. Additionally, no significant immune-mediated damage was detected in the vaccinated animals. In conclusion, the antigenic peptide hR32 vaccine mimicking the (32Asp catalytic site of human renin may constitute a novel tool for the development of a renin vaccine.

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.

Regional blood flows by the microsphere method: reproducibility in portal hypertensive rats and influence of a portal vein catheter

International Nuclear Information System (INIS)

Hadengue, A.; Lee, S.S.; Koshy, A.; Girod, C.; Lebrec, D.

1988-01-01

To determine the reproducibility of splanchnic blood flow measurements by the microsphere method in rats with portal hypertension and the effects of laparotomy with portal vein cannulation, eight groups of 10 rats were studied. Microspheres were labelled with 113 Sn or 141 Ce. Laparotomy with portal cannulation had no significant effect in sham-operated rats. In awake portal hypertensive rats, cardiac output and splanchnic blood flow were lower in portal vein cannulated rats compared with those of non-cannulated animals. In anesthetized portal hypertensive rats blood flows were unaffected by portal cannulation, but arterial pressure and heart rate were elevated. Anesthesia also decreased portal pressure in portal hypertensive rats. We conclude that the microsphere method remains reproducible in portal hypertensive rat models. Laparotomy with portal cannulation can alter systemic and splanchnic hemodynamics in portal hypertensive rats; these effects can also be changed during pentobarbital anesthesia. Regional blood flow measurements in portal hypertensive rats should be performed in animals without portal cannulation and preferably in the awake state

Combating Combination of Hypertension and Diabetes in Different Rat Models

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Talma Rosenthal

2010-03-01

Full Text Available Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD, and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH rats. The use of various drugs, such as angiotensin-converting enzyme (ACE inhibitors (ACEIs, various angiotensin receptor blockers (ARBs, and calcium channel blockers (CCBs, to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

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

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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.

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

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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.

Increased albumin permeation in eyes, aorta, and kidney of hypertensive rats fed galactose

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Tilton, R.G.; LaRose, L.; Chang, K.; Weigel, C.J.; Williamson, J.R.

1986-01-01

These experiments were undertaken to determine whether ingestion of galactose increases albumin permeation in the vasculature of hypertensive rats. 50% dextrin (control) or 50% galactose diets were fed to unilaterally nephrectomized, male Sprague-Dawley rats weighing 200 g. Hypertension (systolic pressure >175 mmHg) was induced by weekly IM injections of 25 mg/kg DOCA and 1% saline drinking water; 3 months later 125 I-albumin permeation was assessed in whole eyes, aorta and kidneys. 125 I-albumin permeation was significantly increased in all 3 tissues of hypertensive rats (n = 9) vs controls (n = 9): aorta (3.30 +/- 0.19 (SD) vs 2.87 +/- 0.14), eye (3.15 +/- 0.14 vs 2.59 +/- 0.11), and kidney (6.58 +/- 0.63 vs 3.85 +/- 0.50). Albumin permeation was increased still further in hypertensive rats fed the galactose diet (n = 8): aorta (3.75 +/- 0.38), eye (3.82 +/- 0.17), and kidney (10.74 +/- 3.13). Hypertension +/- galactose feeding had no effect on albumin permeation in lung, skin, or brain. These findings indicate that: (1) hypertension increases albumin permeation in vessels affected by diabetic vascular diseases, and 2) hypertension-induced increases in albumin permeation are increased still further by galactose ingestion, presumably mediated by imbalances in polyol/insitol metabolism (analogous to those induced by diabetes) independent of hyperglycemia and/or insulinopenia

Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

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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.

Chaos in blood flow control in genetic and renovascular hypertensive rats

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Yip, K P; Holstein-Rathlou, N H; Marsh, D J

1991-01-01

Hydrostatic pressure and flow in renal proximal tubules oscillate at 30-40 mHz in normotensive rats anesthetized with halothane. The oscillations originate in tubuloglomerular feedback, a mechanism that provides local blood flow regulation. Instead of oscillations, spontaneously hypertensive rats...... (SHR) have aperiodic tubular pressure fluctuations; the pattern is suggestive of deterministic chaos. Normal rats made hypertensive by clipping one renal artery had similar aperiodic tubular pressure fluctuations in the unclipped kidney, and the fraction of rats with irregular fluctuations increased...... with time after the application of the renal artery clip. Statistical measures of deterministic chaos were applied to tubular pressure data. The correlation dimension, a measure of the dimension of the phase space attractor generating the time series, indicated the presence of a low-dimension strange...

Antihypertensive effect of rhizome part of Acorus calamus on renal artery occlusion induced hypertension in rats

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Pinal Patel

2012-05-01

Full Text Available Objective: The rhizomes part of Acorus calamus (AC having the calcium inhibitory effect and diuretic activity which may potentiate Na+ excretion in hypertension induced by occlusion of renal artery. Therefore this study was aimed to investigate the effect of AC on experimentally induced hypertension. Methods: Hypertension in rats was induced by clamping the left renal artery for 4h by arterial clamp (2K1C. At the end of experiment animal were anesthetized with ketamine (50 mg/kg. Carotid artery was cannulated which was connected to pressure transducer for estimation of blood pressure. Results: Ethyl acetate extract of Acorus calamus rhizomes (EAAC treated rats that underwent hypertension, demonstrated significant (P < 0.01 lower systolic blood pressure and diastolic blood pressure when compared with 2K1C rats indicated blood pressure lowering activity. Plasma renin activity was significantly (P < 0.05 decreased in EAAC treated rats compared to 2K1C rats. EAAC treated rats that underwent hypertension demonstrated significant (P < 0.01 lower mean blood urea nitrogen and creatinine when compared with 2K1C rats. Lipid peroxidation was significantly (P < 0.001 decreased, where as nitric oxide level in tissue was significantly elevated in EAAC treated rats. Antioxidant enzymes like glutathione, superoxide dismutase and catalase were significantly (P < 0.05, P < 0.01, P < 0.001 increased in EAAC treated rats when compared to 2K1C rats. Conclusions: In conclusions, EAAC treatment attenuated renal artery occlusion induced hypertension via nitric oxide generation and decreases the plasma renin activity.

Spatial Memory in Spontaneously Hypertensive Rats (SHR)

NARCIS (Netherlands)

Sontag, Thomas-A.; Fuermaier, Anselm B. M.; Hauser, Joachim; Kaunzinger, Ivo; Tucha, Oliver; Lange, Klaus W.

2013-01-01

The spontaneously hypertensive rat (SHR) is an established animal model of ADHD. It has been suggested that ADHD symptoms arise from deficits in executive functions such as working memory, attentional control and decision making. Both ADHD patients and SHRs show deficits in spatial working memory.

Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

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Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

1990-01-01

Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

86Rubidium uptake in mononuclear leucocytes from young subjects at increased risk of developing essential hypertension

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Nielsen, J R; Johansen, Torben; Pedersen, K E

1988-01-01

This study was designed to assess any changes in mononuclear leucocytes from young men at increased risk of developing essential hypertension and to determine whether any changes found were associated with borderline hypertension and/or heredity. To this end we used mononuclear leucocytes......, and especially in those borderline hypertensives with at least one hypertensive parent. The latter group was also the group at greatest risk of developing essential hypertension....

Long working hours and risk for hypertension in Japanese male white collar workers.

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Nakanishi, N; Yoshida, H; Nagano, K; Kawashimo, H; Nakamura, K; Tatara, K

2001-05-01

To evaluate the association of long working hours with the risk for hypertension. A five year prospective cohort study. Work site in Osaka, Japan. 941 hypertension free Japanese male white collar workers aged 35-54 years were prospectively examined by serial annual health examinations. Men in whom borderline hypertension and hypertension were found during repeated surveys were defined as incidental cases of borderline hypertension and hypertension. 336 and 88 men developed hypertension above the borderline level and definite hypertension during the 3940 and 4531 person years, respectively. After controlling for potential predictors of hypertension, the relative risk for hypertension above the borderline level, compared with those who worked hours per day, was 0.63 (95% confidence intervals (CI): 0.43, 0.91) for those who worked 10.0-10.9 hours per day and 0.48 (95% CI: 0.31, 0.74) for those who worked > or = 11.0 hours per day. The relative risk for definite hypertension, compared with those who worked hours per day, was 0.33 (95% CI: 0.11, 0.95) for those who worked > or = 11.0 hours per day. The multivariate adjusted slopes of diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) during five years of follow up decreased as working hours per day increased. From the multiple regression analyses, working hours per day remained as an independent negative factor for the slopes of systolic blood pressure, DBP, and MABP. These results indicate that long working hours are negatively associated with the risk for hypertension in Japanese male white collar workers.

Reduction of transmural 125I-albumin concentration in rat aortic media by chronic hypertension

International Nuclear Information System (INIS)

Belmin, J.; Michel, J.B.; Curmi, P.A.; Salzmann, J.L.; Juan, L.; Tedgui, A.

1991-01-01

Relative 125I-albumin concentration was measured in vivo in the aortic media of sham-operated (n = 10) and hypertensive (two-kidney, one clip) rats, untreated (n = 8) or treated (n = 10) by an angiotensin converting enzyme inhibitor (CEI, Trandolapril). Blood pressure was acutely lowered to a normal level at the time of the experiment in hypertensive rats (n = 7) to separate the direct effect of increased pressure from the effect of pressure-induced structural changes. Relative tissue concentration profiles of labeled albumin across the media were obtained using a serial frozen-sectioning technique. In hypertensive rats, the mean medial albumin concentration decreased by 35% in the ascending arch and 32% in the descending arch (p less than 0.01). When blood pressure was acutely lowered in hypertensive animals, this value decreased further by 56% in the ascending arch, 48% in the descending arch (p less than 0.01), and 22% in the thoracic aorta (p less than 0.05) as compared with controls. The medial thickness in hypertensive rats was significantly increased (more in the ascending arch than in the rest of the aorta). Four-week CEI treatment reversed hypertension and medial thickening, but the mean medial albumin concentration remained significantly lower in the arch (by 36% in the ascending part and 40% in the descending part, p less than 0.01). The collagen content in the thoracic aorta was significantly increased in hypertensive rats (by 40%, p less than 0.01) and remained increased (by 29%, p less than 0.01) after CEI treatment. These results suggested that the hypertension-induced structural changes might reduce the medial distribution volume for albumin, whereas elevated blood pressure per se tended to enhance albumin concentration within the media

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

Exploratory studies of some Mexican medicinal plants. Cardiovascular effects in rats with and without hypertension.

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Gil Alfonso Magos-Guerrero

2017-09-01

Full Text Available Background: Papaveraceae Argemone mexicana L., Burseraceae Bursera simaruba (L. Sarg., Acanthaceae Justicia spicigera Schltdl. and Selaginellaceae Selaginella lepidophylla (Hook. & Grev. Spring., have been used in Mexican traditional medicine to treat hypertension. The objective of this study was to further characterize the cardiovascular effects of the methanol extracts of such plants. Methods: The medicinal plants were collected and taxonomically identified; the methanol extract of each explored plant were administrated to conscious and unconscious male Wistar rats with and without glucose induced hypertension. The blood pressure and heart rate were evaluated before and after the extract administration. Vascular reactivity experiments were conducted in rat aortic rings obtained from rats with and without sugar induced hypertension, a model widely used to study such effects with cardiovascular agents. Results: After oral administration in normotensive conscious rats all tested extracts decreased the heart rate, such effect was only observed in hypertensive conscious rats after the administration of B. simaruba; only A. mexicana and B. simaruba decreased the blood pressure after oral administration. All extracts administrated by intravenous injection diminished the mean arterial pressure. Dose response curves to cumulative concentrations of all the extracts promote vascular relaxation in precontracted aortas from rats with and without sugar induced hypertension. Conclusions: The present study indicated that B. simaruba is worthy of further investigation as a potential phytotherapeutic agent for treating hypertension. [J Complement Med Res 2017; 6(3.000: 274-279

Hydronephrosis causes salt-sensitive hypertension in rats

DEFF Research Database (Denmark)

Carlström, Mattias; Wåhlin, Nils; Sällström, Johan

2006-01-01

BACKGROUND: Hypertension is a common disease in the Western world and approximately 5% of all cases are secondary to kidney malfunction. It is not clear whether unilateral hydronephrosis due to partial obstruction affects blood pressure. AIM: The aim of this study was to determine whether...... hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device was implanted 4-6 weeks later and blood pressure was measured...... on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. RESULTS: All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis...

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

International Nuclear Information System (INIS)

Silva, Tharciano Luiz Teixeira Braga da; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim dos Santos; Carvalho, Vitor Oliveira; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana

2015-01-01

Hypertension is a public health problem and increases the incidence of cardiovascular diseases. To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of N G -nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

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Silva, Tharciano Luiz Teixeira Braga da; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim dos Santos; Carvalho, Vitor Oliveira; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Universidade Federal de Sergipe, Universidade de São Paulo (Brazil)

2015-08-15

Hypertension is a public health problem and increases the incidence of cardiovascular diseases. To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of N{sup G}-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

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Tharciano Luiz Teixeira Braga da Silva

2015-01-01

Full Text Available Abstract Background: Hypertension is a public health problem and increases the incidence of cardiovascular diseases. Objective: To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME-induced hypertensive rats. Methods: Wistar rats were divided into three groups: control (C, hypertensive (H, and exercised hypertensive (EH. Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN, potassium chloride (KCl and sodium nitroprusside (SNP. Results: Rats treated with L-NAME showed an increase (p < 0.001 in systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial pressure (MAP compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001 the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01 smooth muscle sensitivity to NPS was observed in group EH as compared to group H. Conclusion: One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

Establishment of a reversible model of prehepatic portal hypertension in rats.

Science.gov (United States)

Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-08-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

The flavonoid quercetin reverses pulmonary hypertension in rats.

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Daniel Morales-Cano

Full Text Available Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH.

The activation of the kynurenine pathway in a rat model with renovascular hypertension.

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Bartosiewicz, Jacek; Kaminski, Tomasz; Pawlak, Krystyna; Karbowska, Malgorzata; Tankiewicz-Kwedlo, Anna; Pawlak, Dariusz

2017-04-01

Hypertension is a serious condition that can lead to many health problems. The mechanisms underlying this process are still not fully understood. The kynurenine pathway may be involved in the occurrence and progression of hypertension. The purpose of this study was to examine the activity of peripheral kynurenine pathway in rats with renovascular hypertension in Goldblatt 2K1C model. Hypertension was induced in the experimental groups by constricting the renal artery of the left kidney of the rats. Determination of tryptophan (Trp) and kynurenine pathway metabolites was assessed by high-performance liquid chromatography in plasma and tissues obtained at 4, 8, and 16 weeks after the surgical intervention or sham surgery. Levels of Ang II were evaluated using commercial immuno-enzymatic ELISA kits. Surgical treatment led to increased values of mean blood pressure and systolic blood pressure, whereas Trp concentrations were decreased in experimental animals compared to appropriate controls. Simultaneously, the considerable increment of kynurenine pathway components and a significant increase in the activity of tryptophan 2,3-dioxygenase were observed in rats with developed hypertension in comparison with controls. There were no differences between Ang II levels in controls and experimental groups. The inverse relationship was between plasma Trp and both SBP and Ang II values, and Trp independently affected Ang II concentrations in hypertensive rats. In contrast, tryptophan 2,3-dioxygenase activity and plasma kynurenine metabolites positively correlated with blood pressure values as well as with Ang II levels in these animals. Moreover, kynurenine was independently connected with MBP. Renovascular hypertension influences kynurenine pathway and leads to an imbalance in Trp and its metabolite levels. Tryptophan 2,3-dioxygenase and part of the kynurenine metabolites in plasma and tissues positively correlated with blood pressure values and Ang II levels. Although the

ANTXR2 Knock-Out Does Not Result in the Development of Hypertension in Rats.

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Liu, Xiaoyan; Yuan, Wen; Li, Jing; Yang, Lei; Cai, Jun

2017-02-01

Our recent genetic study as well as robust evidences reported by previous genome-wide association studies (GWASs) have indicated that the single nucleotide polymorphism rs16998073, located near gene anthrax toxin receptor 2 (ANTXR2), was significantly associated with hypertension in Asians and Europeans. The aim of the present study was to determine whether ANTXR2 is the causal gene of hypertension at the 4q21 locus using an ANTXR2 knock-out model. Relative expression of ANTXR2 in Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were determined by real-time quantitative polymerase chain reaction and western blot analysis. ANTXR2 knock-out rats were created using CRISPR/Cas9-mediated genome editing and blood pressure values were measured in ANTXR2 -/- and wild type (WT) rats by tail-cuff method and carotid arterial catheterization method. Neither the mRNA nor protein levels of ANTXR2 were significantly different between tissues from SHRs and WKYs. To create ANTXR2 -/- rats, 67 base pairs were deleted in exon 1 of ANTXR2 using CRISPR/Cas9-mediated genome editing. ANTXR2 protein decreased significantly in aortas of ANTXR2 -/- rats, suggesting sufficient efficiency of ANTXR2 knock-out in this model. However, ANTXR2 -/- rats exhibited nearly the same blood pressure as WT rats at baseline conditions as well as during Angiotensin II (400ng/kg/min) infusion or high-salt diet treatment. These findings suggest that ANTXR2 might not be associated with hypertension and thus further functional analysis is warranted to identify the causal gene at this locus. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat

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Rabinovitch, M.; Mullen, M.; Rosenberg, H.C.; Maruyama, K.; O'Brodovich, H.; Olley, P.M.

1988-01-01

Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, the authors investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. They instrumented the rats with indwelling cardiovascular catheters and compared the hemodynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. They then determine whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. They observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effects of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both antiotensin II and prostacyclin infusion similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins

Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.

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Black, Mary Jane; D'Amore, Angelo; Auden, Alana; Stamp, Laura; Osicka, Tanya; Panagiotopoulos, Sianna; Jerums, George

2010-01-01

Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats. Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry. Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain. Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition. Copyright © 2010 Elsevier Inc. All rights reserved.

Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by amlodipine

NARCIS (Netherlands)

Blezer, E.L.A.; Nicolaij, K.; Goldschmeding, R.C.; Koomans, H.A.; Joles, Jaap

2002-01-01

Dihydropyridine Ca2+ channel antagonists, initiated together with high salt intake, prevent the development of hypertension and subsequent cerebral damage in stroke-prone spontaneously hypertensive rats (SHRSP). We hypothesized that the dihydropyridine Ca2+ channel antagonist amlodipine

Resistance training controls arterial blood pressure in rats with L-NAME- induced hypertension.

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Araujo, Ayslan Jorge Santos de; Santos, Anne Carolline Veríssimo dos; Souza, Karine dos Santos; Aires, Marlúcia Bastos; Santana-Filho, Valter Joviniano; Fioretto, Emerson Ticona; Mota, Marcelo Mendonça; Santos, Márcio Roberto Viana

2013-04-01

Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (parteries. RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.

Increased proteoglycan synthesis by the cardiovascular system of coarctation hypertensive rats

International Nuclear Information System (INIS)

Lipke, D.W.; Couchman, J.R.

1991-01-01

Proteoglycan (PG) synthesis in the cardiovascular system of coarctation hypertensive rats was examined by in vivo and in vitro labeling of glycosaminoglycans with 35SO4 in rats made hypertensive for short (4 days) and longer (14 days) durations. With in vivo labeling, only tissues directly exposed to elevated pressure (left ventricle, LV and aorta above the clip, AOR increases) exhibited elevated PG synthesis after 4 days of hypertension. By 14 days, tissues both exposed to (LV and AOR increases) and protected from elevated pressure (right ventricle and kidney) exhibited elevated PG synthetic rates. Slight elevations in the proportion of galactosaminoglycans were observed with a concurrent proportional decrease in heparan sulfate PGs. Using the in vitro labeling procedure, no significant increases in PG synthesis were observed in any tissue at either 4 days or 14 days of hypertension. These data indicate that: (1) coarctation hypertension stimulates PG production that is dependent initially on increased pressure and later, on additional non-pressure related factors, (2) these other factors are responsible for enhanced PG production in tissues not directly exposed to pressure overload, (3) pressure and/or these other factors are essential for enhanced PG production in coarctation hypertension, and (4) synthesis of all GAG types appears to be affected

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

DEFF Research Database (Denmark)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting

2016-01-01

Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX......) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal...

Quantitative evaluation of CART-containing cells in urinary bladder of rats with renovascular hypertension

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I. Janiuk

2015-04-01

Full Text Available Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin-angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

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Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

2016-01-01

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

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Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

2012-09-01

What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

OpenAIRE

Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-01-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats...

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

Intrahepatic upregulation of MRTF-A signaling contributes to increased hepatic vascular resistance in cirrhotic rats with portal hypertension.

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Zheng, Lei; Qin, Jun; Sun, Longci; Gui, Liang; Zhang, Chihao; Huang, Yijun; Deng, Wensheng; Huang, An; Sun, Dong; Luo, Meng

2017-06-01

Portal hypertension in cirrhosis is mediated, in part, by increased intrahepatic resistance, reflecting massive structural changes associated with fibrosis and intrahepatic vasoconstriction. Activation of the Rho/MRTF/SRF signaling pathway is essential for the cellular regulatory network of fibrogenesis. The aim of this study was to investigate MRTF-A-mediated regulation of intrahepatic fibrogenesis in cirrhotic rats. Portal hypertension was induced in rats via an injection of CCl 4 oil. Hemodynamic measurements were obtained using a polyethylene PE-50 catheter and pressure transducers. Expression of hepatic fibrogenesis was measured using histological staining. Expression of protein was measured using western blotting. Upregulation of MRTF-A protein expression in the livers of rats with CCl 4 -induced cirrhosis was relevant to intrahepatic resistance and hepatic fibrogenesis in portal hypertensive rats with increased modeling time. Inhibition of MRTF-A by CCG-1423 decelerated hepatic fibrosis, decreased intrahepatic resistance and portal pressure, and alleviated portal hypertension. Increased intrahepatic resistance in rats with CCl 4 -induced portal hypertension is associated with an upregulation of MRTF-A signaling. Inhibition of this pathway in the liver can decrease hepatic fibrosis and intrahepatic resistance, as well as reduce portal pressure in cirrhotic rats with CCl 4 -induced portal hypertension. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Importance of Pulmonary Vein Preferential Fibrosis for Atrial Fibrillation Promotion in Hypertensive Rat Hearts.

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Iwasaki, Yu-Ki; Yamashita, Takeshi; Sekiguchi, Akiko; Hayami, Noriyuki; Shimizu, Wataru

2016-06-01

Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts. Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts. Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (αSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the αSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure. PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The antihypertensive effect of fermented milk in individuals with prehypertension or borderline hypertension

DEFF Research Database (Denmark)

Usinger, Lotte; Jensen, L T; Flambard, B

2010-01-01

 Hg have been reported in spontaneously hypertensive rats fed FM. Results from human studies of the antihypertensive effect are inconsistent. However, many studies suffer from methodological weaknesses, as insufficient blinding and the use of office BP measurements. We conducted a randomised, double......, which could be compatible with a minor antihypertensive effect. Heart rate and lipids remained unchanged between groups. Hence, our study does not support earlier studies measuring office BP-measurements, reporting antihypertensive effect of FM. Based on straight performed 24-h ambulatory BP...

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

Dr. Lewis Kitchener Dahl, the Dahl Rats and the ‘Inconvenient truth’ abou the Genetics of Hypertension

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Joe, Bina

2014-01-01

Synopsis Lewis K. Dahl is regarded as an iconic figure in the field of hypertension research. During the 1960s and 1970s he published several seminal articles in the field that shed light on the relationship between salt and hypertension. Further, the Dahl rat models of hypertension that he developed by a selective breeding strategy are among the most widely used models for hypertension research. To this day, genetic studies using this model are ongoing in our laboratory. While Dr. Dahl is known for his contributions to the field of hypertension, very little, if any, of his personal history is documented. This article details a short biography of Dr. Lewis Dahl, the history behind the development of the Dahl rats and presents an overview of the results obtained through the genetic analysis of the Dahl rat as an experimental model to study the inheritance of hypertension. PMID:25646295

A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.

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Carrie M Elks

Full Text Available To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB have among the highest antioxidant capacities of fruits and vegetables.Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS, peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver assayed in BB-fed rats. These results were evidence of "hormesis" during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group.Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated the potential to delay or attenuate development

Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats

International Nuclear Information System (INIS)

White, S.M.; Wagner, J.G.; Roth, R.A.

1989-01-01

To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. Treatment with PAS on Days 6-8 did not affect the lung injury but resulted in an attenuation of the pulmonary hypertensive response. Pulmonary platelet sequestration was also decreased in PAS-treated rats, yet the sequestration in the lungs of MCTP-treated rats that received PAS was significantly higher than that in the lungs of N,N-dimethylformamide (DMF) controls. MCTP-treated rats receiving control serum (CS) tended to sequester more 111In-labeled platelets than respective DMF controls, but this was not statistically significant. Blood platelet half-life was unaltered in rats receiving CS. When rats were treated similarly with MCTP and PAS and were killed at 18 days, the attenuation of the pulmonary hypertensive response previously described was not observed, and lung injury was more extensive than when CS was given. Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets

Swimming training prevents coronary endothelial dysfunction in ovariectomized spontaneously hypertensive rats

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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.

ALLOPURINOL DOES NOT DECREASE BLOOD PRESSURE OR PREVENT THE DEVELOPMENT OF HYPERTENSION IN THE DOCA-SALT RAT MODEL

Science.gov (United States)

Szasz, Theodora; Linder, A. Elizabeth; Davis, Robert P.; Burnett, Robert; Fink, Gregory D.; Watts, Stephanie W.

2010-01-01

Reactive oxygen species (ROS) play an important role in the pathogenesis of hypertension, disease in which ROS levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a ROS-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on BP have yielded controversial results. We hypothesized that XO inhibition would decrease BP or attenuate the development of DOCA-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg/day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by HPLC measurements of XO metabolites in urine, serum and tissues demonstrating decrease in products, increase in substrates and detection of the active metabolite of allopurinol, oxypurinol. We monitored BP continuously via radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension, regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. PMID:20881613

Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production.

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Blanton, Cynthia; He, Zhengcheng; Gottschall-Pass, Katherine T; Sweeney, Marva I

2015-01-01

Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8) of male spontaneously hypertensive rats were fed one of four AIN '93G-based diets for 8 weeks: Control (CON); 3% freeze-dried wild blueberry (BB); 1% probiotic bacteria (PRO); or 3% BB + 1% PRO (BB+PRO). Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2-isoprostanes), nitric oxide synthesis (nitrites), and polyphenol metabolism (hippuric acid). Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046), with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035). Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220), again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185). Diet had a significant main effect on hippuric acid excretion (pblueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric acid.

Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats

NARCIS (Netherlands)

Blezer, E.L.A.; Nicolaij, K.; Koomans, H.A.; Joles, Jaap

2001-01-01

Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl, show severe hypertension, organ damage, and early death. Preventive treatment with angiotensin II type 1 (AT1) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE)

/sup 86/Rb uptake of various organs of the spontaneously hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Nakamura, M; Kuroiwa, A; Nakagaki, O; Tomoike, H; Nose, Y [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1975-03-01

Twenty spontaneously hypertensive rats (SHR) and 20 control rats were used for the measurement of Rb/sup 86/ uptake by various organs. Hemodynamic measurements, and the heart weight to body weight ratio showed a significant and sustained hypertension with an increased heart rate in SHR. The ratio of the Rb/sup 86/ uptake in the kidney, brain, liver, adrenal gland, pancreas, and spleen to that in the right ventricle (RV) was smaller in SHR than it was in the control rats. The ratio of the Rb/sup 86/ uptake of the inner layer to the outer layer of the left ventricle (LV), which represents distribution of blood flow to the endocardial layer and epicardial layer, showed no difference between SHR and the control rats. The regional flow fraction in the outer and inner cortex, juxtamedulla, and medulla of the kidney showed no difference between SHR and the control. The present preliminary study suggests that the myocardial blood flow in SHR is greater than that in the control rats. The relationship between cardiac hypertrophy and myocardial flow was discussed.

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

Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model

International Nuclear Information System (INIS)

Sikuler, E.; Kravetz, D.; Groszmann, R.J.

1985-01-01

In rats with portal hypertension induced by partial ligation of the portal vein, the authors have recently demonstrated an increased portal venous inflow that becomes an important factor in the maintenance of portal hypertension. The sequence of events that leads into this circulatory disarray is unknown. The authors evaluated chronologically the chain of hemodynamic changes that occurred after portal hypertension was induced by partial ligation of the portal vein. In this model it is possible to follow, from the initiation of the portal-hypertensive state, the interaction between blood flow and resistance in the portal system as well as the relation between the development of portal-systemic shunting and the elevated portal venous inflow. The study was performed in 45 portal-hypertensive rats and in 29 sham-operated rats. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. The constriction of the portal vein was immediately followed by a resistance-induced portal hypertension characterized by increased portal resistance (9.78 +/- 0.89 vs. 4.18 +/- 0.71 dyn X s X cm-5 X 10(4), mean +/- SE, P less than 0.01), increased portal pressure (17.7 +/- 0.9 vs. 9.5 +/- 0.6 mmHg, P less than 0.001), and decreased portal venous inflow (3.93 +/- 0.26 vs. 6.82 +/- 0.49 ml X min-1 X 100 g body wt-1, P less than 0.001)

Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats

DEFF Research Database (Denmark)

Liu, Daoyan; Yang, Dachun; He, Hongbo

2009-01-01

We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by immunohistochem...

The expression of PEDF and VEGF in the gastric wall of prehepatic portal hypertensive rats.

Science.gov (United States)

Pan, Wei-Dong; Liu, Yanzhang; Lin, Nan; Xu, Ruiyun

2011-01-01

Upper gastrointestinal bleeding of portal hypertension cases may result from gastric mucosal lesions due to portal hypertensive gastropathy. The pathological changes in the vessels of the gastric wall are very important in the pathogenesis of portal hypertensive gastropathy. However, the mechanisms of these pathological changes are not completely understood. In this study, we examined the expression levels of PEDF and VEGF in the gastric wall in rats with prehepatic portal hypertension. Eighteen healthy Wistar rats were randomly divided into groups A and B. Group A was used to establish the prehepatic portal hypertensive model and group B to evaluate a sham surgery. The VEGF and PEDF expression in the rat gastric wall were detected by immunohistochemical staining and western blotting. VEGF and PEDF were mainly expressed in the basal layer of the mucosal glands. The expression levels of VEGF and PEDF in group A were higher than that in group B at 7, 10 and 14 days after surgery. The expression levels of VEFG and PEDF in group B did not show significant changes. The results from the present study showed a significantly elevated expression of both VEGF and PEDF in the gastric walls during the development of portal hypertension. The expression of these proteins was mainly located in the basal layer of the gastric mucosa.

Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine

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Sonia Alves Gouvea

2014-01-01

Full Text Available The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM, 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg, denervated normotensive (DN rats, denervated 2K1C (2K1C + DN rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01, whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation.

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

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

Deuterium oxide normalizes blood pressure and vascular calcium uptake in Dahl salt-sensitive hypertensive rats

International Nuclear Information System (INIS)

Vasdev, S.; Prabhakaran, V.; Sampson, C.A.

1990-01-01

This study examined the effect of 25% deuterium oxide in drinking water on systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas of Dahl salt-sensitive rats on 0.4% (low) and 8% (high) sodium chloride (salt) diet. Twenty-four rats were divided into four groups. Groups I and II were on the low salt diet and groups III and IV on the high salt diet from 6 weeks of age. Additionally, at 10 weeks of age groups I and III were placed on 100% water and groups II and IV on 25% deuterium oxide. At 14 weeks, systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas were significantly higher (p less than 0.01) in rats on the high salt diet as compared with those on the low salt diet. Deuterium oxide intake normalized systolic blood pressure and aortic calcium uptake but not aortic rubidium 86 uptake in hypertensive rats on the high salt diet. Deuterium oxide had no effect on blood pressure or aortic calcium uptake in rats on the low salt diet. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in salt-sensitive Dahl rats. Furthermore, deuterium oxide appears to normalize elevated blood pressure in salt-sensitive hypertensive rats by normalizing elevated vascular (aortic) calcium uptake

Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

Science.gov (United States)

Sabaawy, H E; Zhang, F; Nguyen, X; ElHosseiny, A; Nasjletti, A; Schwartzman, M; Dennery, P; Kappas, A; Abraham, N G

2001-08-01

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

Vitamin D3 deficiency increases DNA damage and modify the expression of genes associated with hypertension in normotensive and hypertensive rats

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Carla Silva Machado

2015-05-01

Full Text Available Vitamin D3 is a lipophilic micronutrient obtained from the diet (salmon, sardines, mackerel and cod liver oil or by the conversion of 7-dehydrocholesterol on skin after exposure to UVB radiation. This vitamin participates in several cellular processes, contributes to the maintenance of calcium concentrations, acts on phosphorus absorption, and is also related to the development and progression of chronic diseases. In hypertension, it is known that vitamin D3 act on renin-angiotensin-aldosterone system, regulates the gene expression and can induce or attenuate oxidative DNA damage. Vitamin D3 deficiency is present in 30-50% of human population (Pilz et al., 2009, and has been associated with increase of chromosomal instability and DNA damage (Nair-Shalliker; Armstrong; Fenech, 2012. Since experimental and clinical studies have suggested a relationship between vitamin D3 and blood pressure, the aim of this study was to evaluate whether vitamin D3 deficiency or supplementation lead to an increase or decrease in DNA damage, regulates the expression of genes associated with hypertension and changes the systolic blood pressure. Spontaneously hypertensive rats (SHR, used as a model of human essential hypertension, and their normotensive controls (Wistar Kyoto – WKY were fed a control diet (vitamin D3 at 1.000 UI/kg, a deficient diet (vitamin D3 at 0 UI/kg or a supplemented diet (vitamin D3 at 10.000 UI/kg for 12 weeks. DNA damage was assessed by comet assay in cardiac muscle tissue and blood tissue, following the methodology proposed by Singh et al. (1988 and Tice et al. (2000; gene expression of 84 genes was assessed by RT2ProfilerTM PCR Array in cardiac muscle tissue; and systolic blood pressure was measured weekly by a noninvasive method using tail plethysmography. In SHR and WKY rats, vitamin D3 deficiency increased DNA damage in the blood tissue and did not change the DNA damage in cardiac muscle tissue; vitamin D3 supplementation maintained the

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

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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.

Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model.

Science.gov (United States)

Szasz, Theodora; Linder, A Elizabeth; Davis, Robert P; Burnett, Robert; Fink, Gregory D; Watts, Stephanie W

2010-12-01

Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model.

Cinnamaldehyde Attenuates Cataractogenesis via Restoration of Hypertension and Oxidative Stress in Fructose-Fed Hypertensive rats

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Amrita Singh

2016-06-01

Full Text Available Objectives: Several studies have revealed that systemic hypertension is strongly associated with cataractogenesis. However, the pathophysiology and treatment is often unclear. In this study, we evaluated the anti-cataractogenic effect of cinnamaldehyde (CA, a natural organic compound, in rats with fructose-induced hypertension. Methods: The rats were divided into six groups. For six weeks, the normal group received a suspension of 0.5% carboxy methyl cellulose (10 mL/kg/day, p.o. while five other groups received a 10% (w/v fructose solution in their drinking water to induce hypertension. By the end of the third week hypertension had been induced in all the animals receiving fructose. From the beginning of the fourth week to the end of the sixth week, one of those five groups (control continued to receive only 10% (w/v fructose solution, one group (standard received ramipril (1 mg/kg/day, p.o. plus 10% (w/v fructose solution, and three groups (experimental received CA at doses of 20, 30, and 40 mg/kg/day p.o., plus 10% (w/v fructose solution. Blood pressure was measured weekly using a non-invasive blood pressure apparatus. After six weeks, the animals were sacrificed, and the anti-cataractogenic effects on the eye lenses were evaluated. Results: Administration of fructose elevated both the systolic and the diastolic blood pressures, which were significantly reduced by CA at all dose levels. In the control group, a significant increase in the malonaldehyde (MDA level and decreases in the total protein, Ca2+adenosine triphosphate (ATPase activity, glutathione peroxidase, catalase, superoxide dismutase and glutathione levels, as compared to the normal group, were observed. Administration of CA at all doses significantly restored the enzymatic, non-enzymatic, antioxidants, total protein, and Ca2+ATPase levels, but decreased the MDA level, as compared to the control group. Conclusion: The present study revealed that CA modulated the antioxidant

Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

DEFF Research Database (Denmark)

Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka

2016-01-01

BACKGROUND: Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics......, and compared it to human NCIPH. METHODS: Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one...... in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. DISCUSSION: This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies....

Effects of raloxifene on portal hypertension and hepatic encephalopathy in cirrhotic rats.

Science.gov (United States)

Chang, Ching-Chih; Lee, Wen-Shin; Chuang, Chiao-Lin; Hsin, I-Fang; Hsu, Shao-Jung; Chang, Ting; Huang, Hui-Chun; Lee, Fa-Yauh; Lee, Shou-Dong

2017-05-05

Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

Science.gov (United States)

Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

2017-07-01

In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

OpenAIRE

Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and...

Milan hypertensive rat as a model for studying cation transport abnormality in genetic hypertension

International Nuclear Information System (INIS)

Ferrari, P.; Barber, B.R.; Torielli, L.; Ferrandi, M.; Salardi, S.; Bianchi, G.

1987-01-01

Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinary output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na+-K+ cotransport and passive permeability were faster. The differences in volume, sodium content, and Na+-K+ cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F1 (MHS X MNS) hybrids. Moreover, in normal segregating F2 hybrid populations there was a positive correlation between blood pressure and Na+-K+ cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus, erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension. 35 references

Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model.

Science.gov (United States)

Yang, Hyun; Hwang, Inho; Koo, Tae-Hyoung; Ahn, Hyo-Jin; Kim, Sun; Park, Mi-Jin; Choi, Won-Sil; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2012-02-01

The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model.

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

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Womersley, Jacqueline S; Mpeta, Bafokeng; Dimatelis, Jacqueline J; Kellaway, Lauriston A; Stein, Dan J; Russell, Vivienne A

2016-06-17

Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague-Dawley comparator strains. Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague-Dawley strains but not in Wistar Kyoto rats. Our findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders.

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

Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production.

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Cynthia Blanton

Full Text Available Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8 of male spontaneously hypertensive rats were fed one of four AIN '93G-based diets for 8 weeks: Control (CON; 3% freeze-dried wild blueberry (BB; 1% probiotic bacteria (PRO; or 3% BB + 1% PRO (BB+PRO. Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2-isoprostanes, nitric oxide synthesis (nitrites, and polyphenol metabolism (hippuric acid. Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046, with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035. Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220, again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185. Diet had a significant main effect on hippuric acid excretion (p<0.0001, with 2- and ~1.5-fold higher levels at weeks 4 and 8, respectively, in the BB and BB+PRO vs. PRO and CON groups. Diet did not have a significant main effect on F2-isoprostane (p = 0.159 or nitrite excretion (p = 0.670. Our findings show that adding probiotics to a blueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric

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 - Gene tics ; Molecular Biology OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 4.691, year: 2016

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats

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Campos, Debora Ribeiro; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S.; Ferreira, Luciana Garros; Monteiro, Ariadne Santana e Neves; Coelho, Eduardo Barbosa; Evora, Paulo Roberto Barbosa

2017-01-01

Background The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. Results The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. Conclusion The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects;The chemiluminescence plasmatic NO analysis showed no significant difference between groups andThe Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy. PMID:28678928

Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

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Elliott M McMillan

Full Text Available Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY and spontaneously hypertensive rats (SHR were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG of hypertensive rats had higher (p<0.05 caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05 ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05 Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05 Beclin-1 and ATG7 protein, as well as decreased (p<0.05 caspase-3, calpain, and cathepsin activity. Left ventricle (LV of hypertensive rats had reduced (p<0.05 AMPKα and LC3II protein, as well as elevated (p<0.05 p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05 proteasome activity but reduced (p<0.05 caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats.

Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

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Fedor Simko

2014-01-01

Full Text Available Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day or melatonin (10 mg/kg/day. Exposure to continuous light led to hypertension, left ventricular (LV hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

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

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats.

Science.gov (United States)

Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

2014-08-29

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ 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 Ca2+ 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 Ca2+ 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/F0), 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 Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, 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 left ventricular myocytes.

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

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M.A. Carneiro-Júnior

2014-11-01

Full Text Available In cardiomyocytes, calcium (Ca2+ release units comprise clusters of intracellular Ca2+ 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 Ca2+ 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 Ca2+ 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/F0, 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 Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, 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 left ventricular myocytes.

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

International Nuclear Information System (INIS)

Carneiro-Júnior, M.A.; Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R.; Amadeu, M.A.; Oliveira, E.M.; Felix, L.B.; Cruz, J.S.; Mill, J.G.; Natali, A.J.; Prímola-Gomes, T.N.

2014-01-01

In cardiomyocytes, calcium (Ca 2+ ) release units comprise clusters of intracellular Ca 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 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 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 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 2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F 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 left ventricular myocytes

Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

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Ploj Karolina

2005-09-01

Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. Methods Our objectives in this study were (1 to estimate sympathetic-adrenal medullary (SAM activity by measuring mean systolic blood pressure (MSAP in rats with estradiol valerate (EV-induced PCO; (2 to estimate alpha1a and alpha2a adrenoceptor expression in a brain area thought to mediate central effects on MSAP regulation and in the adrenal medulla; (3 to assess hypothalamic-pituitary-adrenal (HPA axis regulation by measuring adrenocorticotropic hormone (ACTH and corticosterone (CORT levels in response to novel-environment stress; and (4 to measure abdominal obesity, sex steroids, and insulin sensitivity. Results The PCO rats had significantly higher MSAP than controls, higher levels of alpha1a adrenoceptor mRNA in the hypothalamic paraventricular nucleus (PVN, and lower levels of alpha2a adrenoceptor mRNA in the PVN and adrenal medulla. After exposure to stress, PCO rats had higher ACTH and CORT levels. Plasma testosterone concentrations were lower in PCO rats, and no differences in insulin sensitivity or in the weight of intraabdominal fat depots were found. Conclusion Thus, rats with EV-induced PCO develop hypertension and increased sympathetic and HPA-axis activity without reduced insulin sensitivity, obesity, or hyperandrogenism. These findings may have implications for mechanisms underlying hypertension in PCOS.

[Effect of Dendrobium officinale granule on long-term-alcohol-induced hypertension rats].

Science.gov (United States)

Lv, Gui-Yuan; Xia, Chao-Qun; Chen, Su-Hong; Su, Jie; Liu, Xiao-Pang; Li, Bo; Gao, Jian-Li

2013-10-01

To observe the effect of Dendrobium officinale granule (DOG) on symptoms, blood pressure and serum biochemical indexes of long-term-alcohol-induced hypertension rats. The alcohol-induced hypertension rat model was established by feeding alcohol drink to normal rats (the alcohol volume fraction increases from 5% to 22%). Since the 4th week, DOG was administered for 32 weeks, once everyday. During the experiment, body weight, kinematic parameters (locomotor activities, grip strength, duration of vertigo) and blood pressures (systolic blood pressure, diastolic blood pressure and mean blood pressure) were detected regularly. On the 28th and 32nd weeks, blood samples were collected to determine serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), uric acid (UA), creatinine (Cr), cholesterol (CH) and triglycerides (TG). (1) Sign: The DOG-administered group showed reduction in the duration of vertigo and increase in appetite, body weight, locomotor activities and grip strength. (2) Blood pressure: The DOG-administered group showed significant decrease in blood pressure since the 8th week. (3) Biochemical indexes: The DOG-administered group showed notable decrease in serum ALT, AST, ALP, Cr, UA, TG level, but without significant change in TC level. The long-term administration of DOG can relieve alcohol-induced hypertension, while alleviating general signs, liver and kidney injuries and abnormal blood fat biochemical indexes.

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

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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

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 ...

Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short-term hypotensive effect.

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Bądzyńska, B; Sadowski, J

2012-08-01

Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

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Li Jing

2011-11-01

Full Text Available The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2 inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY rats, spontaneously hypertensive rats (SHR and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

Effect of Antioxidant Mineral Elements Supplementation in the Treatment of Hypertension in Albino Rats

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S. A. Muhammad

2012-01-01

Full Text Available Oxidative stress has been implicated in various pathologies, including hypertension, atherosclerosis, diabetes, and chronic renal disease. The current work was designed with the aim of investigating the potentials of antioxidants copper, manganese, and zinc in the treatment of hypertension in Wistar rats. The rats were fed 8% NaCl diet for 5 weeks and treatment with supplements in the presence of the challenging agent for additional 4 weeks. The supplementation significantly decreased the blood pressure as compared with hypertensive control. The result also indicated significant decreased in the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol, malondialdehyde, insulin and increase in the high-density lipoprotein cholesterol, total antioxidant activities, and nitric oxide of the supplemented groups relative to the hypertensive control. The average percentage protection against atherogenesis indicated 47.13 ± 9.60% for all the supplemented groups. The mean arterial blood pressure showed significant positive correlation with glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, insulin resistance and malondialdehyde while high density lipoprotein-cholesterol and total antioxidant activities showed negative correlation. The result therefore indicated strong relationship between oxidative stress and hypertension and underscores the role of antioxidant minerals in reducing oxidative stress, dyslipidemia, and insulin resistance associated with hypertension.

Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat.

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Tardif, Kim; Hertig, Vanessa; Duquette, Natacha; Villeneuve, Louis; El-Hamamsy, Ismail; Tanguay, Jean-François; Calderone, Angelino

2015-05-15

Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark features of vessel remodeling secondary to hypertension. The intermediate filament protein nestin was recently identified in vascular smooth muscle cells and in other cell types directly participated in proliferation. The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid artery- and aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events. Copyright © 2015 the American Physiological Society.

Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats

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Orachorn Boonla

2015-07-01

Full Text Available In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP in a rat model of two kidney-one clip (2K-1C renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg−1 or 100 mg kg−1 or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p < 0.05. Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE, decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p < 0.05. Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity.

Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in Wistar Rats

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Julie Dupas

2017-01-01

Full Text Available Increased sugar consumption, especially fructose, is strongly related to the development of type 2 diabetes (T2D and metabolic syndrome. The aim of this study was to evaluate long term effects of fructose supplementation on Wistar rats. Three-week-old male rats were randomly divided into 2 groups: control (C; n=14 and fructose fed (FF; n=18, with a fructose enriched drink (20–25% w/v fructose in water for 21 weeks. Systolic blood pressure, fasting glycemia, and bodyweight were regularly measured. Glucose tolerance was evaluated three times using an oral glucose tolerance test. Insulin levels were measured concomitantly and insulin resistance markers were evaluated (HOMA 2-IR, Insulin Sensitivity Index for glycemia (ISI-gly. Lipids profile was evaluated on plasma. This fructose supplementation resulted in the early induction of hypertension without renal failure (stable theoretical creatinine clearance and in the progressive development of fasting hyperglycemia and insulin resistance (higher HOMA 2-IR, lower ISI-gly without modification of glucose tolerance. FF rats presented dyslipidemia (higher plasma triglycerides and early sign of liver malfunction (higher liver weight. Although abdominal fat weight was increased in FF rats, no significant overweight was found. In Wistar rats, 21 weeks of fructose supplementation induced a metabolic syndrome (hypertension, insulin resistance, and dyslipidemia but not T2D.

Antihypertensive therapy induces compartment-specific chemokine expression and a Th1 immune response in the clipped kidney of Goldblatt hypertensive rats

NARCIS (Netherlands)

Steinmetz, O. M.; Sadaghiani, S.; Panzer, U.; Krebs, C.; Meyer-Schwesinger, C.; Streichert, T.; Fehr, S.; Hamming, I.; van Goor, H.; Stahl, R. A. K.; Wenzel, U.

The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

Science.gov (United States)

Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

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

International Nuclear Information System (INIS)

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

Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats.

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Shamardl, Hanan A; El-Ashmony, Sahar M; Kamel, Hala F; Fatani, Sameer H

2017-08-01

Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Bladder overdistension with polyuria in a hypertensive rat model.

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Velasquez Flores, Monica; Mossa, Abubakr H; Cammisotto, Philippe; Campeau, Lysanne

2018-03-31

Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology. © 2018 Wiley Periodicals, Inc.

Effect of endurance exercise training on oxidative stress in spontaneously hypertensive rats (SHR) after emergence of hypertension.

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Kimura, Hiroko; Kon, Nobuko; Furukawa, Satoshi; Mukaida, Masahiro; Yamakura, Fumiyuki; Matsumoto, Kazuko; Sone, Hirohito; Murakami-Murofushi, Kimiko

2010-01-01

The purpose of this study is to elucidate the effect of wheel training on oxidative stress maker levels in spontaneous hypertensive rats (SHR). 4-hydroxynonenal and 3-nitrotyrosine levels in the aorta of SHRs were allowed to run for 10 weeks from the age of 15 weeks were measured and compared with those of nonexercised SHRs. The 4-hydroxynonenal and 3-nitrotyrosine levels in the exercised group were significantly lower than those in the nonexercised group. The exercised group showed a significant increase of manganese-containing superoxide dismutase. Endurance exercise showed a possible suppressing effect on the arteriosclerosis development by reducing oxidative stress, even after emergence of hypertension.

Central cardiovascular action of urotensin II in spontaneously hypertensive rats.

Science.gov (United States)

Lin, Yingzi; Tsuchihashi, Takuya; Matsumura, Kiyoshi; Fukuhara, Masayo; Ohya, Yusuke; Fujii, Koji; Iida, Mitsuo

2003-10-01

We have previously reported that urotensin II acts on the central nervous system to increase blood pressure in normotensive rats. In the present study, we have determined the central cardiovascular action of urotensin II in spontaneously hypertensive rats (SHR). Intracerebroventricular (ICV) injection of urotensin II elicited a dose-dependent increase in blood pressure in both SHR and normotensive Wistar-Kyoto rats (WKY). The changes in mean arterial pressure induced by ICV urotensin II at doses of 1 and 10 nmol in the WKY were 8 +/- 2 and 23 +/- 3 mmHg, respectively. ICV administration of urotensin II caused significantly greater increases in blood pressure in SHR (16 +/- 3 mmHg at 1 nmol and 35 +/- 3 mmHg at 10 nmol, respectively) compared with those in WKY. Urotensin II (10 nmol) elicited significant and comparable increases in heart rate in SHR (107 +/- 10 bpm) and WKY (101 +/- 21 bpm). Plasma epinephrine concentrations after ICV administration of 10 nmol urotensin II were 203 +/- 58 pmol/ml in SHR and 227 +/- 47 pmol/ml in WKY, which tended to be higher than those in artificial cerebrospinal fluid-injected rats (73+/- 7 and 87 +/- 28 pmol/ml, respectively, p GPR 14 was expressed extensively in the glial cells within the brainstem, hypothalamus, and thalamus. These results suggest that central urotensin II may play a role in the pathogenesis of hypertension in SHR. Since GPR 14 was expressed in the glial cells of the brain, urotensin II may act as a neuromodulator to regulate blood pressure.

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

Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats

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Rehab F. Abdel-Rahman

2017-01-01

Full Text Available This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive, using N(G-nitro-L-arginine-methyl ester- (L-NAME- induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO, and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence.

Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats.

Science.gov (United States)

Abdel-Rahman, Rehab F; Hessin, Alyaa F; Abdelbaset, Marwan; Ogaly, Hanan A; Abd-Elsalam, Reham M; Hassan, Salah M

2017-01-01

This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive), using N(G)-nitro-L-arginine-methyl ester- (L-NAME-) induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally) for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks) resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO), and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE) and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS) gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence.

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.

Abnormal air righting behaviour in the spontaneously hypertensive rat model of ADHD

OpenAIRE

Dommett, Eleanor J; Rostron, Claire L

2011-01-01

The spontaneously hypertensive rat (SHR) is the most commonly used model of attention-deficit hyperactivity disorder (ADHD), displaying the main symptoms of the disorder which are responsive to psychostimulant treatments. Research to date has focused on behavioural tests investigating functioning of the striatum or prefrontal cortex in these rats. However, there is now evidence that the superior colliculus, a structure associated with head and eye movements, may also be dysfunctional in ADHD....

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

A new rat model of portal hypertension induced by intraportal injection of microspheres

Science.gov (United States)

Li, Xiang-Nong; Benjamin, IS; Alexander, B

1998-01-01

AIM: To produce a new rat model of portal hypertension by intraportal injection of microspheres. METHODS: Measured aliquots of single or different-sized microspheres (15, 40, 80μm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial,portal,hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination. RESULTS: Portal venous pressure was elevated from basal value of 0.89-1.02 kPa to a steady-state of 1.98-3.19 kPa following the sequential injections of single- or different-sized microspheres, with a markedly lowered mean arterial pressure. However, a small-dose injection of 80 μm microspheres (1.8 × 105) produced a steady-state portal venous pressure of 2.53 × 0.17 kPa, and all rats showed normal arterial pressures. In addition, numerous microspheres were found in the lungs in all experimental groups. CONCLUSION: Portal hypertension can be reproduced in rats by intraportal injection of microspheres at a small dose of 80 μm (1.8 × 105). Intrahepatic portal-systemic shunts probably exist in the normal rat liver. PMID:11819236

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

EVALUATION OF SOME ANTIOXIDANTS TREATMENT ON KIDNEY FUNCTION AND LIPID PEROXIDATION STATUS IN HYPERTENSIVE RATS INDUCED WITH L-NAME

International Nuclear Information System (INIS)

MATTA, T.F.

2008-01-01

Hypertension, the disease known as the s ilent killer , is a common problem facing peoples today with million new cases being diagnosed each year. Although a great amount of money is spent annually for the treatment and detection of this disease and its complications, current conventional treatment have done little to reduce the number of patients with hypertension. Research has found a variety of alternative therapies to be successful in reducing high blood pressure including diet, exercise, stress management, supplements and herbs.In this study, the changes in some selected biochemical blood variables, which are thought to represent risk factors coincident with hypertension and kidney function, were compared between a group of normotensive male albino rats and other group suffered from hypertension induced artificially by N-nitro-L-arginine methyl ester (L-NAME). Also, this study investigated the effects of daily administration of some antioxidants nutrients for two weeks namely carnitine, coenzyme Q 1 0 , garlic oil and their mixture on the same variables in order to show to what extent these nutrients are valid to control the levels of these variables without any deleterious effects after treatment. Fifty mg of coenzyme Q 10 and 50 mg of carnitine were daily injected intraperitoneally for two weeks in two groups of hypertensive rats while 200 mg/kg b.wt was given to another group of hypertensive rats by oral intubation. A combination of all the above mentioned nutrients was given to the fourth group. Another hypertensive group was left without any treatment and served as a recovery group. Fasting blood samples were drawn and kidney tissues were taken at the terminal of treatments.The obtained results revealed that induced hypertension caused significant (P<0.05) increase of thiobarbeturic acid reactive substances (TBARs), malondialdehyde (MAD), parathormone (PTH), renin, blood urea, creatinine, phosphorus, sodium and potassium while glutathione (GSH), calcium

Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

1985-01-01

The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125 I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR

Field trial of GABA-fortified rice plants and oral administration of milled rice in spontaneously hypertensive rats.

Science.gov (United States)

Kowaka, Emi; Shimajiri, Yasuka; Kawakami, Kouhei; Tongu, Miki; Akama, Kazuhito

2015-06-01

Hypertension is one of the most critical risk factors accompanying cardiovascular diseases. γ-Aminobutyric acid (GABA) is a non-protein amino acid that functions as a major neurotransmitter in mammals and also as a blood-pressure lowering agent. We previously produced GABA-fortified rice lines of a popular Japonica rice cultivar 'Koshihikari' by genetic manipulation of GABA shunt-related genes. In the study reported here, we grew these same novel rice lines in a field trial and administered the milled rice orally to rats. The yield parameters of the transgenic rice plants were almost unchanged compared to those of untransformed cv. 'Koshihikari' plants, while the rice grains of the transgenic plants contained a high GABA content (3.5 g GABA/kg brown rice; 0.75-0.85 GABA g/kg milled rice) in a greenhouse trial. Oral administration of a diet containing 2.5% GABA-fortified rice, with a daily intake for 8 weeks, had an approximately 20 mmHg anti-hypertensive effect in spontaneous hypertensive rats but not in normotensive Wistar-Kyoto rats. These results suggest that GABA-fortified rice may be applicable as a staple food to control or prevent hypertension.

Arginase promotes endothelial dysfunction and hypertension in obese rats.

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Johnson, Fruzsina K; Peyton, Kelly J; Liu, Xiao-Ming; Azam, Mohammed A; Shebib, Ahmad R; Johnson, Robert A; Durante, William

2015-02-01

This study investigated whether arginase contributes to endothelial dysfunction and hypertension in obese rats. Endothelial function and arginase expression were examined in skeletal muscle arterioles from lean and obese Zucker rats (ZRs). Arginase activity, arginine bioavailability, and blood pressure were measured in lean and obese animals. Arginase activity and expression was increased while global arginine bioavailability decreased in obese ZRs. Acetylcholine or luminal flow caused dilation of isolated skeletal muscle arterioles, but this was reduced or absent in vessels from obese ZRs. Treatment of arterioles with a nitric oxide synthase inhibitor blocked dilation in lean arterioles and eliminated differences among lean and obese vessels. In contrast, arginase inhibitors or l-arginine enhanced vasodilation in obese ZRs and abolished differences between lean and obese animals, while d-arginine had no effect. Finally, mean arterial blood pressure was significantly increased in obese ZRs. However, administration of l-arginine or arginase inhibitors lowered blood pressure in obese but not lean animals, and this was associated with an improvement in systemic arginine bioavailability. Arginase promotes endothelial dysfunction and hypertension in obesity by reducing arginine bioavailability. Therapeutic approaches targeting arginase represent a promising approach in treating obesity-related vascular disease. © 2014 The Obesity Society.

Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.

Science.gov (United States)

Rodríguez-Gómez, Isabel; Manuel Moreno, Juan; Jimenez, Rosario; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Wangensteen, Rosemary; Vargas, Félix

2015-12-01

This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney. The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats. Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nonlinear system analysis of renal autoregulation in normotensive and hypertensive rats

DEFF Research Database (Denmark)

Chon, K H; Chen, Y M; Holstein-Rathlou, N H

1998-01-01

We compared the dynamic characteristics in renal autoregulation of blood flow of normotensive Sprague-Dawley rats (SDR) and spontaneously hypertensive rats (SHR), using both linear and nonlinear systems analysis. Linear analysis yielded only limited information about the differences in dynamics......, NMSE are significantly higher in SHR than SDR, suggesting a more complex nonlinear system in SHR. The contribution of the third-order kernel in describing the dynamics of renal autoregulation in arterial blood pressure and blood flow was found to be important. Moreover, we have identified the presence...

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

Evaluation of the Ca2+ distribution in aortic tissue of spontaneously hypertensive and normotensive rats

International Nuclear Information System (INIS)

Spieker, C.; Zidek, W.; von Bassewitz, D.B.; Heck, D.; Rahn, K.H.

1991-01-01

In the present study, particle-induced X-ray emission (PIXE) was used to get information on the spatial distribution of Ca 2+ in aortas of spontaneously hypertensive rats (SHR) and normotensive controls aged 1 week, 4 weeks, and 12 weeks. To differentiate changes in Ca 2+ metabolism in hypertensive arteries from secondary phenomena due to the arteriosclerosis, the animals were examined in the earliest stage of hypertension. It was found that the Ca 2+ content was not elevated in the aortic smooth muscle of SHR aged 1 week (n = 11), as compared to normotensive controls (n = 10) (186.8 +/- 89.9 micrograms Ca 2+ /g tissue v 254.0 +/- 173.3 micrograms Ca 2+ /g). The Ca 2+ content was raised (P less than .05) in the aortic smooth muscle of SHR aged 4 weeks (n = 13), as compared to 12 WKY rats (4 weeks) (726.0 +/- 130.4 micrograms Ca 2+ /g tissue v 440.3 +/- 214.4 micrograms Ca 2+ /g) and in 17 SHR (3 months), as compared to 13 WKY rats, respectively (3390.1 +/- 729.9 micrograms Ca 2+ /g tissue v 1632.1 +/- 569.5 micrograms Ca 2+ /g). The results confirm the age-related increase in the arterial Ca 2+ content in normotensive rats and demonstrate additionally that this age-related rise in arterial Ca 2+ content is accelerated in SHR

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

Science.gov (United States)

Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

2009-01-01

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners.

Science.gov (United States)

Orescanin, Zorana S; Milovanović, Slobodan R; Spasić, Snezana D; Jones, David R; Spasić, Mihajlo B

2007-01-01

The conversion of nitric oxide (NO*) into its congeners nitrosonium (NO(+)) and nitroxyl (HNO/NO(-)) ions may have important consequences for signal transduction and physiological responses. Manganese-containing superoxide dismutase (MnSOD) may convert NO. into its redox congeners. In our current work, we have examined the mechanism of sodium nitroprusside (SNP)-induced relaxation of arteries, with or without endothelium, from both normotensive and spontaneously hypertensive (SH) rats in the absence and presence of MnSOD. SNP induced a greater degree of relaxation in normotensive than in SH rats. MnSOD antagonized SNP-induced relaxation and effect was greater in normotensive than hypertensive rats. However, MnSOD even potentiated SNP-induced relaxation in mesenteric arteries with endothelium from SH rats. Our results indicate that HNO/NO(-)-mediated relaxation is more effective in mesenteric artery smooth muscle from SH rats than from normotensive rats and that vascular dysfunction in SH rats is not solely endothelium-derived but involves changes in vascular smooth muscles.

Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.

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Decano, Julius L; Pasion, Khristine A; Black, Nicole; Giordano, Nicholas J; Herrera, Victoria L; Ruiz-Opazo, Nelson

2016-01-11

Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and

Permeability of the arterial endothelium of spontaneously hypertensive rats to plasma macromolecules

International Nuclear Information System (INIS)

Yurukova, Z.B.; Georgiev, P.G.

1979-01-01

By means of vascular labelling technique at cellular level, the permeability of the arterial endothelium of spontaneously hypertensive rats has been studied. For this purpose colloidal carbon and plasma lipoproteins were introduced into the jugular vein of the animals. Material for light- and electron-microscopic and radioautographic examinations was taken from the thoracic and abdominal parts of the aorta. The results show that in long-term hypertension substances from plasma enter the aortic wall in increased amounts through two main pathways. First, through the selective physiological pathways of transendothelial transport (through cell junctions and vesicular transport) and secondly, through discontinuities of the endothelial lining (separation of the intercellular junctions, areas of loss of one to several endothelial cells). The alteration of the arterial endothelium barrier function in chronic hypertension seems to be an important mechanism for the progression of hypertensive arterial lesions. (A.B.)

Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agnieszka [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland); Toczek, Marek [Department of Experimental Physiology and Pathophysiology Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok (Poland); Bielawska, Katarzyna [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland); Skrzydlewska, Elżbieta, E-mail: elzbieta.skrzydlewska@umb.edu.pl [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland)

2016-06-15

Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB{sub 1} receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB{sub 1} receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the

Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

International Nuclear Information System (INIS)

Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agnieszka; Toczek, Marek; Bielawska, Katarzyna; Skrzydlewska, Elżbieta

2016-01-01

Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB 1 receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB 1 receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the liver of

Effect of exercise training on Ca²⁺ release units of left ventricular myocytes of spontaneously hypertensive rats.

Science.gov (United States)

Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

2014-11-01

In cardiomyocytes, calcium (Ca²⁺) release units comprise clusters of intracellular Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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/F0), 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 Ca²⁺ sparks=6.26 ± 0.19 µm/s, amplitude=0.282 ± 0.10 ΔF/F0, 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

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

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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.

Stimulation of Intestinal Cl- Secretion Through CFTR by Caffeine Intake in Salt-Sensitive Hypertensive Rats

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Xiao Wei

2018-03-01

Full Text Available Background/Aims: High salt consumption is a major risk factor for hypertension, and sodium homeostasis is regulated by both intestinal sodium absorption and urinary sodium excretion. Chronic caffeine intake has been reported to attenuate salt-sensitive hypertension by promoting urinary sodium excretion; however, its exact role in intestinal sodium absorption remains unknown. Here, we investigated whether and how chronic caffeine consumption antagonizes salt-sensitive hypertension by inhibiting intestinal sodium absorption. Methods: Dahl salt-sensitive rats were fed 8% NaCl chow and 0.1% caffeine in their drinking water for 15 days. The blood pressure and fecal sodium content were measured. The effect of caffeine on the movement of Cl- in enterocyte cells was determined with the Ussing chamber assay. Results: Rats that were treated with caffeine displayed significantly lower mean blood pressure and higher fecal sodium content than the controls. Consistent with these findings, caffeine intake decreased fluid absorption by the intestine in the fluid perfusion experiment. Further, the results from the Ussing chamber assay indicated that caffeine promoted Cl- secretion through enterocyte apical cystic fibrosis transmembrane conductance regulator (CFTR, and thus inhibited sodium absorption. Moreover, depletion of cAMP or inhibition of CFTR completely abolished the effect of caffeine on Cl- secretion. Conclusion: The results indicate that chronic caffeine consumption reduces sodium absorption by promoting CFTR-mediated Cl- secretion in the intestine, which contributes to the anti-hypertensive effect of caffeine in salt-sensitive rats.

Effects of nimodipine on learning in normotensive and spontaneously hypertensive rats.

Science.gov (United States)

Meneses, A; Terrón, J A; Ibarra, M; Hong, E

1997-04-01

It is well known that the calcium channel blocker, nimodipine, has beneficial effects on learning in either aged or hypertensive animals and humans. However, no attempts have been made to investigate if nimodipine can reverse the synergistic deleterious effects of aging and hypertension in the same subject. Therefore, this study investigated the effects of stable infusions of nimodipine in the autoshaping learning task using middle-aged normotensive (WKY) and hypertensive (SHR) rats. WKY and SHR of 12 months of age were implanted with osmotic minipumps releasing either vehicle or nimodipine (0.4 mg/kg/day). After 3 weeks of treatment, the animals received autoshaping training sessions during 4 consecutive days. The WKY animals treated with nimodipine exhibited the highest levels of learning during the last session, the rank order being WKY-nimodipine > SHR-nimodipine > WKY-vehicle > SHR-vehicle. These results confirm that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of both conditions, however, might produce more severe dysfunctional changes that cannot be totally reversed by nimodipine.

Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension.

Science.gov (United States)

Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka; Schierwagen, Robert; Uschner, Frank Erhard; Strassburg, Christian P; Fischer, Hans-Peter; Spengler, Ulrich; Trebicka, Jonel

2016-01-01

Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics, and compared it to human NCIPH. Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one week after last embolization), hemodynamics were investigated, hepatic fibrosis and accumulation of myofibroblasts were analysed. General characteristics, laboratory analyses and liver histology were collected in patients with NCIPH. Weekly embolization induced a hyperdynamic circulation, with increased PP. The mesenteric flow and hepatic hydroxyproline content was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volumes increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies.

Japanese traditional miso soup attenuates salt-induced hypertension and its organ damage in Dahl salt-sensitive rats.

Science.gov (United States)

Yoshinaga, Mariko; Toda, Natsuko; Tamura, Yuki; Terakado, Shouko; Ueno, Mai; Otsuka, Kie; Numabe, Atsushi; Kawabata, Yukari; Uehara, Yoshio

2012-09-01

We investigated the effects of long-term miso soup drinking on salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. Dahl S rats were divided into four groups that consumed 1) water, 2) a 0.9% NaCl solution, 3) a 1.3% sodium NaCl solution, or 4) miso soup containing 1.3% NaCl. They were followed for 8 wk. Systolic blood pressure and hypertensive organ damage were determined. Systolic blood pressure increased in an age- and dose-dependent manner in Dahl S rats drinking salt solutions. The systolic blood pressure increase was significantly less in the Dahl S rats that drank miso soup, although the ultimate cumulative salt loading was greater than that in the Dahl S rats given the 1.3% NaCl solution. This blood pressure decrease was associated with a morphologic attenuation of glomerular sclerosis in the kidney and collagen infiltration in the heart. Urinary protein excretions were less in the miso group than in the rats given the 1.3% NaCl solution. The fractional excretion of sodium was increased and that of potassium was decreased in Dahl S rats given the 1.3% NaCl solution, and these effects were reversed in rats given miso soup toward the values of the control. We found that long-term miso soup drinking attenuates the blood pressure increase in salt-induced hypertension with organ damage. This may be caused by a possible retardation of sodium absorption in the gastrointestinal tract or by the direct effects of nutrients in the miso soup from soybeans. The decrease was associated with decreases in cardiovascular and renal damage. Copyright © 2012 Elsevier Inc. All rights reserved.

Prevalence of dyslipidemia and associated factors among the hypertensive population from rural Northeast China.

Science.gov (United States)

Yu, Shasha; Yang, Hongmei; Guo, Xiaofan; Zhang, Xingang; Zheng, Liqiang; Sun, Yingxian

2015-11-21

Our latest study reported the grim status of hypertension in rural China with the prevalence of hypertension reached 51.1%. However, we lack the latest data about the prevalence and epidemiological features of dyslipidemia among hypertensive residents in rural China. A cross-sectional survey was conducted from July 2012 to August 2013 through a cluster multistage sampling to a resident group of 4048 individuals (2152 men, 2896 women) with hypertension, age ≥ 35 years, in the rural Northeast China. Serum lipids level were proposed by National Cholesterol Education Program Adult Treatment Panel III. Of the hypertension residents without antihypertension treatment, 34.5% had borderline high total cholesterol, 19.2% had high total cholesterol, 11.4% had low high-density lipoprotein cholesterol and 37.4% had high non HDL-C. The population with borderline high, high, and very high low-density lipoprotein cholesterol was 20.9, 6.7 and 2.3%, respectively. In addition, 14.3% had borderline high triglycerides, 17.4% had high TG and 2.4% had very high TG. The awareness rate of dyslipidemia among the study population was 5.9%. After adjusting for independent variables, fasting plasma glucose, body mass index, Han nationality, current drinking and smoking, higher annual income and classification of blood pressure were risk factors for dyslipidemia while moderate physical activity was protective factor for dyslipidemia. On the contrary, gender and current drinking decrease the risk of HDL-C. The prevalence of dyslipidemia was dramatically high and dyslipidemia screening was in-need in all diagnosed hypertensive individuals.

Increased arterial smooth muscle Ca2+ signaling, vasoconstriction, and myogenic reactivity in Milan hypertensive rats

Science.gov (United States)

Linde, Cristina I.; Karashima, Eiji; Raina, Hema; Zulian, Alessandra; Wier, Withrow G.; Hamlyn, John M.; Ferrari, Patrizia; Blaustein, Mordecai P.

2012-01-01

The Milan hypertensive strain (MHS) rats are a genetic model of hypertension with adducin gene polymorphisms linked to enhanced renal tubular Na+ reabsorption. Recently we demonstrated that Ca2+ signaling is augmented in freshly isolated mesenteric artery myocytes from MHS rats. This is associated with greatly enhanced expression of Na+/Ca2+ exchanger-1 (NCX1), C-type transient receptor potential (TRPC6) protein, and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) compared with arteries from Milan normotensive strain (MNS) rats. Here, we test the hypothesis that the enhanced Ca2+ signaling in MHS arterial smooth muscle is directly reflected in augmented vasoconstriction [myogenic and phenylephrine (PE)-evoked responses] in isolated mesenteric small arteries. Systolic blood pressure was higher in MHS (145 ± 1 mmHg) than in MNS (112 ± 1 mmHg; P arteries from MHS rats had significantly augmented myogenic tone and reactivity and enhanced constriction to low-dose (1–100 nM) PE. Isolated MHS arterial myocytes exhibited approximately twofold increased peak Ca2+ signals in response to 5 μM PE or ATP in the absence and presence of extracellular Ca2+. These augmented responses are consistent with increased vasoconstrictor-evoked sarcoplasmic reticulum (SR) Ca2+ release and increased Ca2+ entry, respectively. The increased SR Ca2+ release correlates with a doubling of inositol 1,4,5-trisphosphate receptor type 1 and tripling of SERCA2 expression. Pressurized MHS arteries also exhibited a ∼70% increase in 100 nM ouabain-induced vasoconstriction compared with MNS arteries. These functional alterations reveal that, in a genetic model of hypertension linked to renal dysfunction, multiple mechanisms within the arterial myocytes contribute to enhanced Ca2+ signaling and myogenic and vasoconstrictor-induced arterial constriction. MHS rats have elevated plasma levels of endogenous ouabain, which may initiate the protein upregulation and enhanced Ca2+ signaling. These

Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

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Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

2013-11-30

l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1μM; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4μM; n=5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. Copyright © 2013 Elsevier Inc. All rights reserved.

Degenerative effects in rat eyes after experimental ocular hypertension

Directory of Open Access Journals (Sweden)

G. Scarsella

2012-10-01

Full Text Available This study was used to evaluate the degenerative effects on the retina and eye-cup sections after experimental induction of acute ocular hypertension on animal models. In particular, vascular events were directly focused in this research in order to assess the vascular remodeling after transient ocular hypertension on rat models. After local anaesthesia by administration of eye drops of 0.4% oxibuprocaine, 16 male adult Wistar rats were injected in the anterior chamber of the right eye with 15 µL of methylcellulose (MTC 2% in physiological solution. The morphology and the vessels of the retina and eye-cup sections were examined in animals sacrificed 72 h after induction of ocular hypertension. In retinal fluorescein angiographies (FAGs, by means of fluorescein isothiocyanate-coniugated dextran (FITC, the radial venules showed enlargements and increased branching, while the arterioles appeared focally thickened. The length and size of actually perfused vessels appeared increased in the whole superficial plexus. In eye-cup sections of MTC-injected animals, in deep plexus and connecting layer there was a bigger increase of vessels than in controls. Moreover, the immunolocalization of astrocytic marker glial fibrillary acidic protein (GFAP revealed its increased expression in internal limiting membrane and ganglion cell layer, as well as its presence in Müller cells. Finally, the pro-angiogenic factor vascular endothelial growth factor (VEGF was found to be especially expressed by neurones of ganglion cell layer, both in control and in MTC-injected eyes. The data obtained in this experimental model on the interactions among glia, vessels and neurons should be useful to evaluate if also in glaucomatous patients the activation of vessel-adjacent glial cells might play key roles in following neuronal dysfunction.

Degenerative effects in rat eyes after experimental ocular hypertension.

Science.gov (United States)

Scarsella, G; Nebbioso, M; Stefanini, S; Pescosolido, N

2012-10-08

This study was used to evaluate the degenerative effects on the retina and eye-cup sections after experimental induction of acute ocular hypertension on animal models. In particular, vascular events were directly focused in this research in order to assess the vascular remodeling after transient ocular hypertension on rat models. After local anaesthesia by administration of eye drops of 0.4% oxibuprocaine, 16 male adult Wistar rats were injected in the anterior chamber of the right eye with 15 µL of methylcellulose (MTC) 2% in physiological solution. The morphology and the vessels of the retina and eye-cup sections were examined in animals sacrificed 72 h after induction of ocular hypertension. In retinal fluorescein angiographies (FAGs), by means of fluorescein isothiocyanate-coniugated dextran (FITC), the radial venules showed enlargements and increased branching, while the arterioles appeared focally thickened. The length and size of actually perfused vessels appeared increased in the whole superficial plexus. In eye-cup sections of MTC-injected animals, in deep plexus and connecting layer there was a bigger increase of vessels than in controls. Moreover, the immunolocalization of astrocytic marker glial fibrillary acidic protein (GFAP) revealed its increased expression in internal limiting membrane and ganglion cell layer, as well as its presence in Müller cells. Finally, the pro-angiogenic factor vascular endothelial growth factor (VEGF) was found to be especially expressed by neurones of ganglion cell layer, both in control and in MTC-injected eyes. The data obtained in this experimental model on the interactions among glia, vessels and neurons should be useful to evaluate if also in glaucomatous patients the activation of vessel-adjacent glial cells might play key roles in following neuronal dysfunction.

Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

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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.

Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

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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.

Blood pressure responses to LBNP in nontrained and trained hypertensive rats

Science.gov (United States)

Bedford, T. G.; Tipton, C. M.

1992-01-01

To study the influences of 16 wk of endurance training on the reflex regulation of resting blood pressure, nontrained (NT) and trained (T) female hypertensive rats (SHR) were subjected to conditions of lower body negative pressure (LBNP). Measurements of muscle cytochrome oxidase activity and run time to exhaustion indicated that the animals were endurance trained. The rats (NT = 6, T = 7) were tranquilized with 300-600 micrograms.kg-1 diazepam (IV) before heart rates and blood pressures were measured over a range of 2.5-10.0 mm Hg of negative pressure. When subjected to conditions of LBNP, the reflex tachycardia of the T group was greater than the NT at the lower (-2.5 and -5.0 mm Hg) negative pressures. Although arterial pressure declines were similar in both groups, the T group experienced significantly less of a decline in central venous pressure than the NT animals. When chlorisondamine was used as a ganglionic blocker (2.5 mg.kg-1, IV), the fall in CVP at 10 mm Hg negative pressure was greater for the NT group while the fall in the initial systemic arterial pressure was more for the T group. From these results we concluded that training had altered the interaction between cardiopulmonary and arterial baroreflexes in these hypertensive rats and a nonneural component had been altered such as cardiac function.

Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress.

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Ravingerová, T; Bernátová, I; Matejíková, J; Ledvényiová, V; Nemčeková, M; Pecháňová, O; Tribulová, N; Slezák, J

2011-01-01

Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Science.gov (United States)

Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-09-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Myocardial myostatin in spontaneously hypertensive rats with heart failure.

Science.gov (United States)

Damatto, R L; Lima, A R R; Martinez, P F; Cezar, M D M; Okoshi, K; Okoshi, M P

2016-07-15

Myostatin has been shown to regulate skeletal and cardiac muscle growth. However, its status on long-term hypertrophied myocardium has not been addressed. The purpose of this study was to evaluate the expression of myocardial myostatin and its antagonist follistatin in spontaneously hypertensive rats (SHR) with heart failure. Eighteen-month-old SHR were evaluated to identify clinical features of heart failure such as tachypnea/labored respiration and weight loss. After heart failure was detected, rats were subjected to echocardiogram and euthanized. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting. Statistical analysis was performed by Student's t test. All SHR (n=8) presented right ventricular hypertrophy and five had lung congestion. SHR had left chambers hypertrophy and dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17mm; p=0.004; left ventricular (LV) diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7mm/kg; p=0.001), and LV systolic dysfunction (midwall fractional shortening: WKY 34.9±3.31; SHR 24.8±3.20%; p=0.003). Myocyte diameter (WKY 23.1±1.50, SHR 25.5±1.33μm; p=0.004) and myocardial interstitial collagen fraction (WKY 4.86±0.01; SHR 8.36±0.02%; pMyostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) expression was lower in SHR. Myostatin and follistatin expression negatively correlated with LV diastolic diameter-to-body weight ratio and LV systolic diameter, and positively correlated with midwall fractional shortening. Myostatin and follistatin protein expression is reduced in the long-term hypertrophied myocardium from spontaneously hypertensive rats with heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Characterization of rat lines with normotensive and hypertensive status using genomic fingerprinting

NARCIS (Netherlands)

Adarichev, V A; Korokhov, N P; Ostapchuk, Ia V; Dymshits, G M; Markel', A L; Ostaptchouk, Jana

1996-01-01

The properties of normotensive and hypertensive rat lines were investigated by the DNA fingerprinting method using a multilocus micro-satellite (CAC)5 probe. The HaeIII and HinfI restriction endonucleases were found to be the most informative enzymes in this case. The high genetic homogeneity of the

Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats.

Science.gov (United States)

Koriyama, Hiroshi; Nakagami, Hironori; Nakagami, Futoshi; Osako, Mariana Kiomy; Kyutoku, Mariko; Shimamura, Munehisa; Kurinami, Hitomi; Katsuya, Tomohiro; Rakugi, Hiromi; Morishita, Ryuichi

2015-07-01

Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. The aim of this study was to design DNA vaccines for high blood pressure and eventually develop human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months. Systolic blood pressure was consistently lower in hepatitis B core-Ang II group after immunization, whereas blood pressure reduction was continued for at least 6 months. Perivascular fibrosis in heart tissue was also significantly decreased in hepatitis B core-Ang II group. Survival rate was significantly improved in hepatitis B core-Ang II group. This study demonstrated that Ang II DNA vaccine to spontaneously hypertensive rats significantly lowered high blood pressure for at least 6 months. In addition, Ang II DNA vaccines induced an adequate humoral immune response while avoiding the activation of self-reactive T cells, assessed by ELISPOT assay. Future development of DNA vaccine to treat hypertension may provide a new therapeutic option to treat hypertension. © 2015 American Heart Association, Inc.

Detection of acute myocardial infarction in spontaneously hypertensive rats by /sup 99m/Tc-Pyrrolidino methyl tetracycline

Energy Technology Data Exchange (ETDEWEB)

Zmbova, B; Tadzer, I; Stakic, D; Bogdanova, V; Stojanova, D

1983-01-01

The myocardial infarct induced by isoproterenol in spontaneously hypertensive rats accumulates higher activities of /sup 99/sup(m)Tc-PM tetracycline compared with the cardiac infarct in normotensive rats caused by the same method. The isoproterenol model of the myocardial necrosis was induced in intact rats without opening the thorax and is a convenient method for experimental radioisotope studies.

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

Directory of Open Access Journals (Sweden)

Victoria L M Herrera

Full Text Available The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01 and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37 and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28, all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

Science.gov (United States)

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of

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.

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

Energy Technology Data Exchange (ETDEWEB)

Simplicio, Janaina A. [Programa de Pós-Graduação em Farmacologia - Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP (Brazil); Departamento de Enfermagem Psiquiátrica e Ciências Humanas - Laboratório de Farmacologia - Escola de Enfermagem de Ribeirão Preto (USP), Ribeirão Preto, SP (Brazil); Simão, Marilia R.; Ambrosio, Sergio R. [Núcleo de Pesquisa em Ciências e Tecnologia - Universidade de Franca (UNIFRAN), Franca, SP (Brazil); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Departamento de Enfermagem Psiquiátrica e Ciências Humanas - Laboratório de Farmacologia - Escola de Enfermagem de Ribeirão Preto (USP), Ribeirão Preto, SP (Brazil)

2016-06-15

Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.

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.

Expression of testicular angiotensin-converting enzyme in adult spontaneously hypertensive rats.

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Genka Krasteva

2009-05-01

Full Text Available Recent studies demonstrated that one isoform of angiotensin-converting enzyme named testicular or germinal (tACE is localized in postmeiotic male germ cells and is essential for fertilizing ability of spermatozoa. Hypertension in spontaneously hypertensive rats (SHR is androgen-dependent and reduction in male gametes is reported in this experimental conditions. Expression of tACE was not studied under conditions of spontaneous hypertension. The aim of this work is to characterize immuno-expression of tACE in the testis of adult (16-week-old SHR rats in relation to the changes in blood pressure and serum testosterone level. In 82% of adult SHR, the immuno-expression of tACE followed the normal stage-specific pattern. Destructive testicular changes, germ cells depletion have been observed in 18% of 16-week-old SHR and stronger expression of tACE in stages 8-11 compared to controls was detected. As a result stage specificity in SHR was not as evident as in control. No reaction was found in germ cell depleted tubules in which elongated spermatids were absent. Degenerating germ cells exhibited strong immunostaining comparable to that in residual bodies. The blood pressure was significantly higher in SHR and testosterone levels were more than twice but non-significantly elevated. There was no clear correlation between testicular structural changes, blood pressure level values or serum testosterone levels. Expression of tACE in postmeiotic germ cells, specifically altered by SHR, suggested possible involvement of components of renin-angiotensin system in the process of spermiogenesis. Loss of enzyme expression we found in germ cell depleted tubules in SHR is due to absence of corresponding stages of spermatid differentiation. Therefore, tACE can be used as a marker for germ cell depletion due to hypertension and other pathological conditions.

Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

Science.gov (United States)

Matrai, Mate; Hetthéssy, Judit R; Nadasy, Gyorgy L; Szekacs, Bela; Mericli, Metin; Acs, Nandor; Monos, Emil; Arbib, Nissim; Varbiro, Szabolcs

2016-07-01

Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

The increased concentration of 2,3-diphosphoglycerate in red blood cells of spontaneously hypertensive rats.

Science.gov (United States)

Przybylski, J; Skotnicka-Fedorowicz, B; Lisiecka, A; Siński, M; Abramczyk, P

1997-12-01

It has been recognised that high haemoglobin oxygen capacity is essential for the development of high blood pressure in spontaneously hypertensive rats. In the present study we have found increased concentration of 2,3 diphosphoglycerate (2,3-DPG) in red blood cells of spontaneously hypertensive rats (SHR) of Okamoto-Aoki strain. As 2,3-DPG is the major factor decreasing haemoglobin affinity to oxygen, our finding suggests that at given value of pO2 oxygen delivery to the tissue of SHR would be increased. Therefore increased concentration of 2,3-DPG in red blood cells of SHR would be of the pathophysiological meaning by promoting autoregulatory increase in total vascular resistance in this strain of rats. The mechanism responsible for enhanced synthesis of 2,3-DPG in SHR remains unclear. Intracellular alkalosis due to either hypocapnia and/or an enhanced activity of Na+/H+ antiporter occurring in SHR are the most plausible explanations for the above finding.

Entrainment of Spontaneously Hypertensive Rat Fibroblasts by Temperature Cycles

Science.gov (United States)

Sládek, Martin; Sumová, Alena

2013-01-01

The functional state of the circadian system of spontaneously hypertensive rats (SHR) differs in several characteristics from the functional state of normotensive Wistar rats. Some of these changes might be due to the compromised ability of the central pacemaker to entrain the peripheral clocks. Daily body temperature cycles represent one of the important cues responsible for the integrity of the circadian system, because these cycles are driven by the central pacemaker and are able to entrain the peripheral clocks. This study tested the hypothesis that the aberrant peripheral clock entrainment of SHR results from a compromised peripheral clock sensitivity to the daily temperature cycle resetting. Using cultured Wistar rat and SHR fibroblasts transfected with the circadian luminescence reporter Bmal1-dLuc, we demonstrated that two consecutive square-wave temperature cycles with amplitudes of 2.5°C are necessary and sufficient to restart the dampened oscillations and entrain the circadian clocks in both Wistar rat and SHR fibroblasts. We also generated a phase response curve to temperature cycles for fibroblasts of both rat strains. Although some of the data suggested a slight resistance of SHR fibroblasts to temperature entrainment, we concluded that the overall effect it too weak to be responsible for the differences between the SHR and Wistar in vivo circadian phenotype. PMID:24116198

Danshensu prevents hypoxic pulmonary hypertension in rats by inhibiting the proliferation of pulmonary artery smooth muscle cells via TGF-β-smad3-associated pathway.

Science.gov (United States)

Zhang, Ning; Dong, Mingqing; Luo, Ying; Zhao, Feng; Li, Yongjun

2018-02-05

Hypoxic pulmonary hypertension is characterized by the remodeling of pulmonary artery. Previously we showed that tanshinone IIA, one lipid-soluble component from the Chinese herb Danshen, ameliorated hypoxic pulmonary hypertension by inhibiting pulmonary artery remodeling. Here we explored the effects of danshensu, one water-soluble component of Danshen, on hypoxic pulmonary hypertension and its mechanism. Rats were exposed to hypobaric hypoxia for 4 weeks to develop hypoxic pulmonary hypertension along with administration of danshensu. Hemodynamics and pulmonary arterial remodeling index were measured. The effects of danshensu on the proliferation of primary pulmonary artery smooth muscle cells and transforming growth factor-β-smad3 pathway were assessed in vitro. Danshensu significantly decreased the right ventricle systolic pressure, the right ventricle hypertrophy and pulmonary vascular remodeling index in hypoxic pulmonary hypertension rats. Danshensu also reduced the increased expression of transforming growth factor-β and phosphorylation of smad3 in pulmonary arteries in hypoxic pulmonary hypertension rats. In vitro, danshensu inhibited the hypoxia- or transforming growth factor-β-induced proliferation of primary pulmonary artery smooth muscle cells. Moreover, danshensu decreased the hypoxia-induced expression and secretion of transforming growth factor in primary pulmonary adventitial fibroblasts and NR8383 cell line, inhibited the hypoxia or transforming growth factor-β-induced phosphorylation of smad3 in rat primary pulmonary artery smooth muscle cells. These results demonstrate that danshensu ameliorates hypoxic pulmonary hypertension in rats by inhibiting the hypoxia-induced proliferation of pulmonary artery smooth muscle cells, and the inhibition effects is associated with transforming growth factor-β-smad3 pathway. Therefore danshensu may be a potential treatment for hypoxic pulmonary hypertension. Copyright © 2017 Elsevier B.V. All rights

Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

DEFF Research Database (Denmark)

Neves, S R S; Machado, C R S; Pinto, A M T

2006-01-01

The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions a...

Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats

Science.gov (United States)

Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

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

Science.gov (United States)

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.

Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

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W.A. Rocha

2010-04-01

Full Text Available Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR. Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks were assigned to three groups: SHR-Cap (N = 51 treated with captopril (1 g/L in drinking water from the 4th to the 14th week; SHR-C (N = 48 untreated SHR; Wistar (N = 47 control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 ± 3 vs 136 ± 5 mmHg, LVH (2.17 ± 0.05 vs 2.97 ± 0.14 mg/g body weight and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 ± 0.01 vs 0.26 ± 0.02 μm² (SHR-Cap vs SHR-C. However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 ± 2 mmHg, 2.50 ± 0.06 mg/g, 0.27 ± 0.02 μm². Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

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Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

2016-10-01

Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

Science.gov (United States)

Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

Renal hypertension prevents run training modification of cardiomyocyte diastolic Ca2+ regulation in male rats.

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Palmer, B M; Lynch, J M; Snyder, S M; Moore, R L

2001-06-01

The combined effects of endurance run training and renal hypertension on cytosolic Ca2+ concentration ([Ca2+]c) dynamics and Na+-dependent Ca2+ regulation in rat left ventricular cardiomyocytes were examined. Male Fischer 344 rats underwent stenosis of the left renal artery [hypertensive (Ht), n = 18] or a sham operation [normotensive (Nt), n = 20]. One-half of the rats from each group were treadmill trained for >16 wk. Cardiomyocyte fura 2 fluorescence ratio transients were recorded for 7 min during electrical pacing at 0.5 Hz, 2 mM extracellular Ca2+ concentration, and 29 degrees C. The rate of [Ca2+]c decline was not changed by run training in the Nt group but was reduced in the Ht group. At 7 min, cardiomyocytes were exposed to 10 mM caffeine in the absence of Na+ and Ca2+, which triggered sarcoplasmic reticular Ca2+ release and suppressed Ca2+ efflux via Na+/Ca2+ exchanger. External Na+ was then added, and Na+-dependent Ca2+ efflux rate was recorded. Treadmill training significantly enhanced Na+-dependent Ca2+ efflux rate under these conditions in the Nt group but not in the Ht group. These data provide evidence that renal hypertension prevents the normal run training-induced modifications in diastolic [Ca2+]c regulation mechanisms, including Na+/Ca2+ exchanger.

Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

NARCIS (Netherlands)

Fowler, Ewan D.; Benoist, David; Drinkhill, Mark J.; Stones, Rachel; Helmes, Michiel; Wüst, Rob C. I.; Stienen, Ger J. M.; Steele, Derek S.; White, Ed

2015-01-01

Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control

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...

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model.

Science.gov (United States)

Li, Jian; Niu, Jian-Zhao; Wang, Ji-Feng; Li, Yu; Tao, Xiao-Hua

2005-11-07

To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, Pportal vein were significantly higher in model group than those in the control group. Plasma HA (129.97+/-16.10 vs 73.09+/-2.38 ng/mL, Pmodel group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs 0.032+/-0.004, Pprotein level (0.152+/-0.005 vs 0.029+/-0.005, Pmodel group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, Pprotein expression (3.015+/-1.364 vs 0.446+/-0.009, Pmodel group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, Pportal hypertension in rats.

Locomotor activity and catecholamine receptor binding in adult normotensive and spontaneously hypertensive rats

International Nuclear Information System (INIS)

Hellstrand, K.; Engel, J.

1980-01-01

The binding of 3 H-WB 4101, an α 1 -adrenoceptor antagonist, the membranes of the cerebral cortex, the hypothalamus, and the lower brainstem was examined in adult spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) controls. The specific binding of 3 H-WB 4101 (0.33 nM) was significantly higher in homogenates from the cerebral cortex of SH rats as compared to WK rats. No differences were detected between SH and WK rats in the specific binding of 3 H-spiroperidol (0.25 nM), a dopamine receptor antagonist, to membranes from the corpus striatum and the limbic forebrain. The locomotor activity was significantly higher in SH rats as compared to WK controls, in all probability due to a lack of habituation to environmental change. It is suggested that the high reactivity of SH rats is related to a disfunction in the noradrenergic neurons in the central nervous system. (author)

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

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

Science.gov (United States)

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.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats.

Science.gov (United States)

Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats*

Science.gov (United States)

Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; de Almeida, Francine Maria; da Silva, Bárbara Soares; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation. PMID:25210965

Blockade of TGF-β 1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

Directory of Open Access Journals (Sweden)

José Luis Miguel-Carrasco

2012-01-01

Full Text Available NADPH oxidases constitute a major source of superoxide anion (⋅O2 - in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1.

Exercise training lowers the enhanced tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats.

Science.gov (United States)

Zha, Yan-Ping; Wang, Yang-Kai; Deng, Yu; Zhang, Ru-Wen; Tan, Xing; Yuan, Wen-Jun; Deng, Xiao-Ming; Wang, Wei-Zhong

2013-04-01

It is well known that low-intensity exercise training (ExT) is beneficial to cardiovascular dysfunction in hypertension. The tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM), a key region for control of blood pressure and sympathetic tone, has been demonstrated to be increased in hypertensive rats. The aim of this study was to determine the effect of ExT on the increased glutamatergic input to the RVLM in spontaneously hypertensive rat (SHR). Normotensive rats Wistar-Kyoto (WKY) and SHR were treadmill trained or remained sedentary (Sed) for 12 weeks and classed into four groups (WKY-Sed, WKY-ExT, SHR-Sed, and SHR-ExT). The release of glutamate in the RVLM and its contribution to cardiovascular activity were determined in WKY and SHR after treatment of ExT. Blood pressure and sympathetic tone were significantly reduced in SHR after treatment with ExT. Bilateral microinjection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nL) into the RVLM significantly decreased resting blood pressure, heart rate, and renal sympathetic nerve activity in SHR-Sed but not in WKY groups (WKY-Sed and WKY-ExT). However, the degree of reduction in these cardiovascular parameters evoked by KYN was significantly blunted in SHR-ExT compared with SHR-Sed group. The concentration of glutamate and the protein expression of vesicular glutamate transporter 2 in the RVLM were significantly increased in SHR-Sed compared with WKY-Sed, whereas they were reduced after treatment with ExT. Our findings suggest that ExT attenuates the enhancement in the tonically acting glutamatergic input to the RVLM of hypertensive rats, thereby reducing the sympathetic hyperactivity and blood pressure. © 2013 Blackwell Publishing Ltd.

Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats

OpenAIRE

Stephen P. Chelko; Chad W. Schmiedt; Tristan H. Lewis; Tom P. Robertson; Stephen J. Lewis

2014-01-01

This study compared the contractile responses elicited by angiotensin II (AII), arginine vasopressin (AVP), and 5-hydroxytryptamine (5-HT) in isolated occipital arteries (OAs) from sham-operated (SHAM) and 2-kidney, 1-clip (2K-1C) hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery) and distal segments (closer to the nodose ganglion) and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, hea...

Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat.

Directory of Open Access Journals (Sweden)

Ali Ashek

Full Text Available Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage. Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ≈ 20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone.

Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

Science.gov (United States)

Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

2015-03-01

The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Inhibition of Mammalian Target of Rapamycin Complex 1 Attenuates Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.

Science.gov (United States)

Kumar, Vikash; Wollner, Clayton; Kurth, Theresa; Bukowy, John D; Cowley, Allen W

2017-10-01

The goal of the present study was to explore the protective effects of mTORC1 (mammalian target of rapamycin complex 1) inhibition by rapamycin on salt-induced hypertension and kidney injury in Dahl salt-sensitive (SS) rats. We have previously demonstrated that H 2 O 2 is elevated in the kidneys of SS rats. The present study showed a significant upregulation of renal mTORC1 activity in the SS rats fed a 4.0% NaCl for 3 days. In addition, renal interstitial infusion of H 2 O 2 into salt-resistant Sprague Dawley rats for 3 days was also found to stimulate mTORC1 activity independent of a rise of arterial blood pressure. Together, these data indicate that the salt-induced increases of renal H 2 O 2 in SS rats activated the mTORC1 pathway. Daily administration of rapamycin (IP, 1.5 mg/kg per day) for 21 days reduced salt-induced hypertension from 176.0±9.0 to 153.0±12.0 mm Hg in SS rats but had no effect on blood pressure salt sensitivity in Sprague Dawley treated rats. Compared with vehicle, rapamycin reduced albumin excretion rate in SS rats from 190.0±35.0 to 37.0±5.0 mg/d and reduced the renal infiltration of T lymphocytes (CD3 + ) and macrophages (ED1 + ) in the cortex and medulla. Renal hypertrophy and cell proliferation were also reduced in rapamycin-treated SS rats. We conclude that enhancement of intrarenal H 2 O 2 with a 4.0% NaCl diet stimulates the mTORC1 pathway that is necessary for the full development of the salt-induced hypertension and kidney injury in the SS rat. © 2017 American Heart Association, Inc.

Aerobic exercise training improves oxidative stress and ubiquitin proteasome system activity in heart of spontaneously hypertensive rats.

Science.gov (United States)

de Andrade, Luiz Henrique Soares; de Moraes, Wilson Max Almeida Monteiro; Matsuo Junior, Eduardo Hiroshi; de Orleans Carvalho de Moura, Elizabeth; Antunes, Hanna Karen Moreira; Montemor, Jairo; Antonio, Ednei Luiz; Bocalini, Danilo Sales; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Brum, Patricia Chakur; Medeiros, Alessandra

2015-04-01

The activity of the ubiquitin proteasome system (UPS) and the level of oxidative stress contribute to the transition from compensated cardiac hypertrophy to heart failure in hypertension. Moreover, aerobic exercise training (AET) is an important therapy for the treatment of hypertension, but its effects on the UPS are not completely known. The aim of this study was to evaluate the effect of AET on UPS's activity and oxidative stress level in heart of spontaneously hypertensive rats (SHR). A total of 53 Wistar and SHR rats were randomly divided into sedentary and trained groups. The AET protocol was 5×/week in treadmill for 13 weeks. Exercise tolerance test, non-invasive blood pressure measurement, echocardiographic analyses, and left ventricle hemodynamics were performed during experimental period. The expression of ubiquitinated proteins, 4-hydroxynonenal (4-HNE), Akt, phospho-Akt(ser473), GSK3β, and phospho-GSK3β(ser9) were analyzed by western blotting. The evaluation of lipid hydroperoxide concentration was performed using the xylenol orange method, and the proteasomal chymotrypsin-like activity was measured by fluorimetric assay. Sedentary hypertensive group presented cardiac hypertrophy, unaltered expression of total Akt, phospho-Akt, total GSK3β and phospho-GSK3β, UPS hyperactivity, increased lipid hydroperoxidation as well as elevated expression of 4-HNE but normal cardiac function. In contrast, AET significantly increased exercise tolerance, decreased resting systolic blood pressure and heart rate in hypertensive animals. In addition, the AET increased phospho-Akt expression, decreased phospho-GSK3β, and did not alter the expression of total Akt, total GSK3β, and ubiquitinated proteins, however, significantly attenuated 4-HNE levels, lipid hydroperoxidation, and UPS's activity toward normotensive group levels. Our results provide evidence for the main effect of AET on attenuating cardiac ubiquitin proteasome hyperactivity and oxidative stress in SHR

Potential benefits of some antioxidant nutrients in reducing the high levels of some biochemical variables associated with induced hypertension in rats

International Nuclear Information System (INIS)

Heibashy, M.I.A.; Abdel-Moneim, A.E.

2005-01-01

In a preliminary trial, the changes in selected biochemical blood variables which are thought to represent risk factors coincident with hypertension were compared between a group of normal control male albino rats (normotensive) and other group suffered from hypertension induced artificially by N-nitro-L-arginine methyl ester (L-NAME). Also, in this study, the effects of four antioxidant nutrients on the same variables were tested in order to show to what extent these nutrients are valid to control the levels of these variables without any deleterious effects after treatment. Co-enzyme Q 10 , taurine or carnitine were daily injected intraperitoneally for two weeks to three groups of hypertensive rats with doses of 50, 500 and 50 mg/kg, respectively. Garlic oil (200 mg / kg) was given to another hypertensive rats by oral intubation. The fourth group received a combination of all the above mentioned nutrients. Another hypertensive group was left without any treatment and served as recovery group. Fasting blood samples were drawn at 2 and 4 weeks after the terminal of the treatments. The results obtained revealed that the induced hypertension caused significant (P<0.001) increase of blood lactate dehydrogenase (LDH), creatin phosphokinase (CPK), aspartate aminotransferase (AST), total nitric oxide (NO), endothelin-1, angiotensin- II, total cholesterol (T Chol), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) as compared with their relevant levels in the control normotensive rats which injected with normal saline. All nutrients used had significant (P<0.05) lowering effects on the activities of serum cardiac enzymes (LDH and CPK) besides AST, but the reduction was more evident when a combination of all nutrients was used as compared with their corresponding levels of the recovery hypertensive group. As a function of interval, the activities of all enzymes were declined significantly (P<0.05) with the advancement of time. The same

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

Unprovoked atrial tachyarrhythmias in aging spontaneously hypertensive rats: the role of the autonomic nervous system.

Science.gov (United States)

Scridon, Alina; Gallet, Clément; Arisha, Moussa M; Oréa, Valérie; Chapuis, Bruno; Li, Na; Tabib, Alain; Christé, Georges; Barrès, Christian; Julien, Claude; Chevalier, Philippe

2012-08-01

Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious, ambulatory animals are lacking. We hypothesized that the aging, spontaneously hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk-old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats. Quantification of AT and heart rate variability (HRV) analysis were performed based on 24-h ECG recordings in unrestrained rats. All animals were submitted to an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were also performed. Spontaneous AT episodes were observed in all eight aging SHRs (median, 91.5; range, 4-444 episodes/24 h), but not in young SHRs or WKY rats. HRV analysis demonstrated significantly decreased low frequency components in aging SHRs compared with age-matched WKY rats (P aging (P = 0.01) SHRs compared with normotensive controls. In aging SHRs, emotional stress significantly reduced the number of arrhythmic events, whereas carbamylcholine triggered AT and significantly increased atrial electrical instability. This study reports the occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and their increased incidence with aging. Our results suggest that autonomic imbalance with relative vagal hyperactivity may be responsible for the increased atrial arrhythmogenicity observed in this model. We also provide evidence that, in this model, the sympatho-vagal imbalance preceded the occurrence of arrhythmia. These results indicate that aging SHRs may provide valuable insight into the understanding of atrial arrhythmias.

Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats.

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Szasz, Theodora; Watts, Stephanie W

2010-06-01

Uric acid (UA) results from xanthine oxidase (XO) catabolism of xanthine and is the final product of purine catabolism in humans. In this species, hyperuricemia is associated with gout, nephropathy, and increased cardiovascular disease risk. Although the effects of hyperuricemia in vascular biology are overall controversial, UA has been described as an antioxidant and as potentially improving endothelial function. Hypertension is associated with endothelial dysfunction. We hypothesized that UA improves the endothelial function of aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. UA (100 microM) in the presence of the uricase inhibitor oxonic acid (10 microM) did not modify relaxation to acetylcholine (ACh) (1 nM-10 microM) in the aorta from nontreated, sham normotensive, and DOCA-salt hypertensive rats [response to 10 microM ACh for UA versus vehicle, respectively: nontreated = 37 +/- 7 versus 48 +/- 7%, sham = 53 +/- 15 versus 57 +/- 20%, DOCA = 81 +/- 4 versus 85 +/- 2% from 20 microM prostaglandin 2alpha (PGF(2alpha))-induced contraction]. Allopurinol (100 microM), a XO inhibitor, did not significantly alter the ACh-induced relaxation of sham and DOCA aortic rings (response to 10 microM ACh for allopurinol versus vehicle, respectively: sham = 61 +/- 5 versus 68 +/- 9%, DOCA = 87 +/- 6 versus 88 +/- 3% from 20 microM PGF(2alpha)-induced contraction). Uricemia, ranging from unmeasurable to 547 microM in sham and to 506 microM in DOCA rats, was not significantly different between these two groups. The expression and activity of XO, as well as the expression of uricase, were not different between sham and DOCA rat aorta. We conclude that, at least in vitro, UA does not affect the ACh-induced relaxation of normotensive and DOCA-salt hypertensive rats.

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

Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution.

Science.gov (United States)

Hsu, Shao-Jung; Tsai, Ming-Hung; Chang, Ching-Chih; Hsieh, Yu-Hsin; Huang, Hui-Chun; Lee, Fa-Yauh; Chuang, Chiao-Ling; Hou, Ming-Chih; Lee, Shou-Dong

2018-03-30

Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague-Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

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Igor Bastos Polonio

2014-08-01

Full Text Available We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH. Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model; and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days Mean pulmonary artery pressure (mPAP was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

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.

Arterial scleroproteins in atherosclerosis and hypertension (Experimental studies)

International Nuclear Information System (INIS)

Yurukova, Ts.; Georgiev, P.

1979-01-01

The authors studied the neosynthesis of fiber protein (scleroproteins) in the aorta of rats with genetic hypertension and with experimental atherosclerosis following application of 3 H-proline and 3 H-lysine and subsequent determination of radioactivity of the collagen and elastic fractions of the aortic wall. There was a great increase in incorporation of labelled collagen and elastin precursors in the aorta of hypertensive and atherosclerotic animals, in comparison with the control rats - a manifestation of incresed ''de novo'' synthesis of fiber proteins in rats with these arterial diseases. Furthermore, the increased collagenosis dominated over that of elastogenesis. The irregular activation of the biosynthesis of both scleroproteins in hypertensive rats and in rats with atherosclerosis caused remodelling of the macromolecular structure of the arterial wall with predominance of collagen over the remaining hypertension components and progression of atherosclerosis. (author) (author)

Blood in the gastric lumen increases splanchnic blood flow and portal pressure in portal-hypertensive rats.

Science.gov (United States)

Chen, L; Groszmann, R J

1996-10-01

In portal-hypertensive humans, portal blood flow and pressure increase after a meal. These hemodynamic changes may increase variceal rupture risk. The aim of this study was to determine whether blood in the stomach lumen increases splanchnic flow and portal pressure (PP) in portal-hypertensive rats. superior mesenteric artery flow and PP were measured in conscious, unrestrained, fasted partial portal vein-ligated rats with chronically implanted Doppler flow probes or portal vein catheters before and after gavage with heparinized, warmed blood from donor rats, air, standard meal, or empty tube. Percentage of changes in flow and pressure from baseline were significantly greater after gavage with blood (an increase of 22.6% +/- 3.5% and an increase of 16.4% +/- 3.1%, respectively) than empty tube (an increase of 3.4% +/- 0.6% and a decrease of 5.4% +/- 3.5%, respectively) (P empty tube (P calories probably contributes to these hemodynamic changes. In patients with variceal hemorrhage, blood in the stomach may increase the risk of persistent variceal bleeding or rebleeding.

Lectin histochemistry and alkaline phosphatase activity in the pia mater vessels of spontaneously hypertensive rats (SHR).

Science.gov (United States)

Szumańska, G; Gadamski, R

1992-01-01

Some lectins were used to study the localization of sugar residues on the endothelial cell surface in the pia mater blood vessels of control (WKY) and hypertensive rats (SHR). The lectins tested recognized the following residues: beta-D-galactosyl (Ricinus communis agglutinin 120, RCA-1), alpha-L-fucosyl (Ulex europaeus agglutinin, UEA-1), N-acetylglucosaminyl and sialyl (Wheat germ agglutinin, WGA), N-glycolyl-neuraminic acid (Limax flavus agglutinin, LFA), and N-acetyl-D-galactosaminyl (Helix pomatia agglutinin, HPA). Several differences were revealed in the presence of sugar receptors on the surface of endothelial cells between the control and the hypertensive rats. Our studies showed also differences in the localization of the tested glycoconjugates between pial capillaries, small, medium-size and large pial arteries. The histochemical evaluation of alkaline phosphatase revealed an increased activity of the enzyme in the pial vessels of SHRs as compared with control rats with a similar localization of the enzyme activity. Some differences in the distribution of lectin binding sites and alkaline phosphatase activity could be associated with the different functions of particular segments of the pial vascular network.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

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T.R. Oliveira

2009-09-01

Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Alpha and beta-adrenoceptors in hypertension. I. Cardiac and renal alpha 1-, beta 1-, and beta 2-adrenoceptors in rat models of acquired hypertension

NARCIS (Netherlands)

Michel, M. C.; Kanczik, R.; Khamssi, M.; Knorr, A.; Siegl, H.; Beckeringh, J. J.; Brodde, O. E.

1989-01-01

To determine whether adrenoceptor changes in genetic hypertension occur primary or secondary to blood pressure elevation, we measured cardiac and renal alpha 1- (by [125I]Be 2254 binding) and beta 1- and beta 2-adrenoceptors (by (-)-[125I]iodocyanopindolol binding) densities in various rat models of

Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

Science.gov (United States)

Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

2016-01-15

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

Science.gov (United States)

Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

2017-08-15

Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

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

A novel vascular clip design for the reliable induction of 2-kidney, 1-clip hypertension in the rat.

Science.gov (United States)

Chelko, Stephen P; Schmiedt, Chad W; Lewis, Tristan H; Lewis, Stephen J; Robertson, Tom P

2012-02-01

The 2-kidney, 1-clip (2K1C) model has provided many insights into the pathogenesis of renovascular hypertension. However, studies using the 2K1C model often report low success rates of hypertension, with typical success rates of just 40-60%. We hypothesized that these low success rates are due to fundamental design flaws in the clips traditionally used in 2K1C models. Specifically, the gap widths of traditional silver clips may not be maintained during investigator handling and these clips may also be easily dislodged from the renal artery following placement. Therefore, we designed and tested a novel vascular clip possessing design features to maintain both gap width and position around the renal artery. In this initial study, application of these new clips to the left renal artery produced reliable and consistent levels of hypertension in rats. Nine-day application of clips with gap widths of 0.27, 0.25, and 0.23 mm elicited higher mean arterial blood pressures of 112 ± 4, 121 ± 6, and 135 ± 7 mmHg, respectively (n = 8 for each group), than those of sham-operated controls (95 ± 2 mmHg, n = 8). Moreover, 8 out of 8 rats in each of the 0.23 and 0.25 mm 2K1C groups were hypertensive, whereas 7 out of 8 rats in the 0.27 mm 2K1C group were hypertensive. Plasma renin concentrations were also increased in all 2K1C groups compared with sham-operated controls. In summary, this novel clip design may help eliminate the large degree of unreliability commonly encountered with the 2K1C model.

Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

Science.gov (United States)

Khan, Shanzana I; Andrews, Karen L; Jackson, Kristy L; Memon, Basimah; Jefferis, Ann-Maree; Lee, Man K S; Diep, Henry; Wei, Zihui; Drummond, Grant R; Head, Geoffrey A; Jennings, Garry L; Murphy, Andrew J; Vinh, Antony; Sampson, Amanda K; Chin-Dusting, Jaye P F

2018-05-01

The essential role of the Y chromosome in male sex determination has largely overshadowed the possibility that it may exert other biologic roles. Here, we show that Y-chromosome lineage is a strong determinant of perivascular and renal T-cell infiltration in the stroke-prone spontaneously hypertensive rat, which, in turn, may influence vascular function and blood pressure (BP). We also show, for the first time to our knowledge, that augmented perivascular T-cell levels can directly instigate vascular dysfunction, and that the production of reactive oxygen species that stimulate cyclo-oxygenase underlies this. We thus provide strong evidence for the consideration of Y-chromosome lineage in the diagnosis and treatment of male hypertension, and point to the modulation of cardiovascular organ T-cell infiltration as a possible mechanism that underpins Y- chromosome regulation of BP.-Khan, S. I., Andrews, K. L., Jackson, K. L., Memon, B., Jefferis, A.-M., Lee, M. K. S., Diep, H., Wei, Z., Drummond, G. R., Head, G. A., Jennings, G. L., Murphy, A. J., Vinh, A., Sampson, A. K., Chin-Dusting, J. P. F. Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats

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Dengfeng Gao

2012-01-01

Full Text Available Objective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males were randomly divided into 3 groups (n=8 each for treatment: pioglitazone (10 mg/kg/day, hydralazine (25 mg/kg/day, or saline. Normal male Wistar Kyoto (WKY rats (n=8 served as normal controls. Twelve weeks later, we evaluated the effect of pioglitazone on vascular fibrosis by Masson’s trichrome and immunohistochemical staining of collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA.Vascular expression of PPAR-γ and connective tissue growth factor (CTGF and transforming growth factor-β (TGF-β expression were evaluated by immunohistochemical staining, western blot analysis, and real-time RT-PCR. Results. Pioglitazone and hydralazine treatment significantly decreased systolic blood pressure in SHRs. Masson’s trichrome staining for collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA indicated that pioglitazone significantly inhibited extracellular matrix production in the aorta. Compared with Wistar Kyoto rats, SHRs showed significantly increased vascular CTGF expression. Pioglitazone treatment significantly increased PPAR-γ expression and inhibited CTGF expression but had no effect on TGF-β expression. Conclusions. The results indicate that pioglitazone attenuated vascular fibrosis in SHRs by inhibiting CTGF expression in a TGF-β-independent mechanism.

Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats

DEFF Research Database (Denmark)

Carlström, M.; Wåhlin, N.; Skøtt, Ole

2007-01-01

shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. METHODS: Partial unilateral ureteral...... obstruction was created in 3-week-old male Sprague-Dawley rats and blood pressure was measured telemetrically 4-6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral...... nephrectomy. RESULTS: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 +/- 15 microGU mL(-1) vs. 96 +/- 12 microGU mL(-1), respectively...

Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Gulati, A.; Bhargava, H.N.

1990-01-01

The binding of [ 3 H] DAMGO, a highly selective ligand for μ-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. [ 3 H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B max value) and apparent dissociation constant (K d value) of [ 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 max value of [ 3 H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K d values in the two strains did not differ. On the other hand, the B max value of [ 3 H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K d values in the two strains were similar

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

Science.gov (United States)

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.

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

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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.

Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats.

Science.gov (United States)

Afkir, Saida; Nguelefack, Telesphore Benoit; Aziz, Mohamed; Zoheir, Johar; Cuisinaud, Guy; Bnouham, Mohamed; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Lahlou, Saad; Ziyyat, Abderrahim

2008-03-05

Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

Hypertension and left ventricular hypertrophy in liquidators of consequences of the Chernobyl nuclear accident

International Nuclear Information System (INIS)

Shal'nova, S.A.; Smolenskij, A.V.; Shamarin, V.M.; Ehktova, T.V.; Berzak, N.V.; Zemtsova, N.A.; Timofeeva, S.G.; Zhavoronkova, E.A.; Muromtseva, G.A.; Arkad'eva, M.A.; Deev, A.D.

1998-01-01

Echocardiography was used for the study of prevalence of left ventricular hypertrophy in 839 liquidators of consequences of the Chernobyl accident. Prevalence of left ventricular hypertrophy (left ventricular myocardial mass 134 g/m 2 ) was 10.3, 13.4 and 22.5 % in liquidators with normal blood pressure, borderline hypertension and hypertension, respectively. Liquidators with normal blood pressure had significantly greater left ventricular myocardial mass than normotensive men from general population while liquidators and non liquidators with hypertension had equal values of this parameter [ru

Chronic Blockade of Brain Endothelin Receptor Type-A (ETA Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats

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Luis R. Cassinotti

2018-02-01

Full Text Available Overactivity of the sympathetic nervous system and central endothelins (ETs are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA-salt hypertensive rats. Following brain ET receptor type A (ETA blockade by BQ610 (selective antagonist, transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ETA blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein in the right OB of hypertensive animals. However, ETA blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ETA are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats.

Science.gov (United States)

Cassinotti, Luis R; Guil, María J; Schöller, Mercedes I; Navarro, Mónica P; Bianciotti, Liliana G; Vatta, Marcelo S

2018-02-27

Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ET A ) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ET A blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ET A blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ET A are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

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You-Lin eTain

2015-12-01

Full Text Available Prenatal dexamethasone (DEX exposure and high-fat (HF intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS, to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification.

Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

OpenAIRE

Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

2015-01-01

Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In ...

Renoprotective effect of virgin coconut oil in heated palm oil diet-induced hypertensive rats.

Science.gov (United States)

Kamisah, Yusof; Ang, Shu-Min; Othman, Faizah; Nurul-Iman, Badlishah Sham; Qodriyah, Hj Mohd Saad

2016-10-01

Virgin coconut oil, rich in antioxidants, was shown to attenuate hypertension. This study aimed to investigate the effects of virgin coconut oil on blood pressure and related parameters in kidneys in rats fed with 5-times-heated palm oil (5HPO). Thirty-two male Sprague-Dawley rats were divided into 4 groups. Two groups were fed 5HPO (15%) diet and the second group was also given virgin coconut oil (1.42 mL/kg, oral) daily for 16 weeks. The other 2 groups were given basal diet without (control) and with virgin coconut oil. Systolic blood pressure was measured pre- and post-treatment. After 16 weeks, the rats were sacrificed and kidneys were harvested. Dietary 5HPO increased blood pressure, renal thiobarbituric acid reactive substance (TBARS), and nitric oxide contents, but decreased heme oxygenase activity. Virgin coconut oil prevented increase in 5HPO-induced blood pressure and renal nitric oxide content as well as the decrease in renal heme oxygenase activity. The virgin coconut oil also reduced the elevation of renal TBARS induced by the heated oil. However, neither dietary 5HPO nor virgin coconut oil affected renal histomorphometry. In conclusion, virgin coconut oil has a potential to reduce the development of hypertension and renal injury induced by dietary heated oil, possibly via its antioxidant protective effects on the kidneys.

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

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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.

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

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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.

Effects of Asian dust event particles on inflammation markers in peripheral blood and bronchoalveolar lavage in pulmonary hypertensive rats

International Nuclear Information System (INIS)

Lei, Y.-C.; Chan, C.-C.; Wang, P.-Y.; Lee, C.-T.; Cheng, T.-J.

2004-01-01

The health impact of dust events from China has become a concern within China and in its neighboring countries. Previous epidemiological studies have demonstrated an association between particulate matter exposure and cardiopulmonary mortality. Here, we use pulmonary hypertensive rat models to examine inflammation markers in the lung and in peripheral blood after exposure to Asian dust storm particles. Using a nose-only inhalation system, eight pulmonary hypertensive rats were exposed to concentrated ambient particles (CAPs) from an actual Asian dust storm that took place between March 18 and 19, 2002; four control rats were also exposed to room air. Four rats exposed to CAPs of 315.6 μg/m 3 for 6 h were classified as the low-exposure group, and another four rats exposed to CAPs of 684.5 μg/m 3 for 4.5 h were classified as the high-exposure group. The animals were sacrificed 36 h after exposure. Inflammation markers in the peripheral blood and in the bronchoalveolar lavage (BAL) were analyzed, and IL-6 in BAL was also determined using ELISA. White blood cell counts in peripheral blood increased with increased CAP exposure levels (P<0.001, test for trend). In BAL analysis, total cell numbers and the proportion of neutrophil also increased with increased CAP levels (P<0.001, test for trend for both markers). Positive dose-response relationships between CAP exposure and total protein (P<0.05) and between CAPs and LDH activity (P<0.05) were also observed. Moreover, IL-6 protein in BAL increasing with CAP levels (P<0.05, test for trend) was demonstrated. Our results revealed that exposure to particulate matters during an Asian dust storm could increase lung inflammation and injury in pulmonary hypertensive rats. Further studies are needed to determine the components of dust storm particles that may contribute to the particle toxicity

Impact of obesity on hypertension-induced cardiac remodeling: role of oxidative stress and its modulation by gemfibrozil treatment in rats.

Science.gov (United States)

Singh, Randhir; Singh, Amrit Pal; Singh, Manjeet; Krishan, Pawan

2011-01-15

This study investigated the possible synergistic role of obesity in hypertension-induced cardiac remodeling and its modulation by gemfibrozil treatment in rats. Male Wistar rats were fed a high-fat diet (HFD) for 90 days. Normal rats were subjected to hypertension by partial abdominal aortic constriction (PAAC) for 28 days. In the HFD+PAAC control group, rats on HFD were subjected to PAAC on the 62nd day and were sacrificed on the 90th day. HFD and PAAC individually resulted in significant cardiac hypertrophy and fibrosis along with increased oxidative stress and mean arterial blood pressure (MABP) in rats as evidenced by various morphological, biochemical, and histological parameters. Moreover, the HFD + PAAC control group showed marked cardiac remodeling compared to rats subjected to HFD or PAAC alone. The HFD+gemfibrozil and HFD+PAAC+gemfibrozil groups showed significant reduction in cardiac remodeling along with reduction in oxidative stress and MABP. Hence, it may be concluded that oxidative stress plays a key role in obesity-mediated synergistic effects on induction and progression of PAAC-induced cardiac remodeling, and its deleterious effects could be reversed by gemfibrozil treatment in rats through its antioxidant activity. Copyright © 2010 Elsevier Inc. All rights reserved.

Portal hypertension and liver cirrhosis in rats: effect of the β3-adrenoceptor agonist SR58611A

Science.gov (United States)

Vasina, Valentina; Giannone, Ferdinando; Domenicali, Marco; Latorre, Rocco; Berzigotti, Annalisa; Caraceni, Paolo; Zoli, Marco; De Ponti, Fabrizio; Bernardi, Mauro

2012-01-01

BACKGROUND AND PURPOSE β3-Adrenoceptors participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β3-adrenoceptors on portal pressure (PP) and systemic haemodynamics and their expression in the liver and mesenteric vessels of cirrhotic rats. EXPERIMENTAL APPROACH PP, central venous pressure (CVP) and systemic haemodynamics were invasively assessed in control and CCl4-treated cirrhotic rats before and during infusion of the selective β3-adrenoceptor agonist, SR58611A. Tissue samples were also collected from liver, heart, portal vein and mesenteric artery for immunohistochemistry and molecular biology analysis. The effect of SR58611A on isolated portal vein was assessed. KEY RESULTS At baseline, cirrhotic rats showed portal hypertension, reduced CVP and hyperdynamic circulation. SR58611A induced a significant, dose-dependent decrease in PP in cirrhotic rats, but not in controls. Although both groups manifested a dose-dependent reduction in mean arterial pressure, this effect was associated with decreased cardiac index (CI) and unchanged indicized peripheral vascular resistance (PVRI) in cirrhotic rats and increased CI and decreased PVRI in control animals. Pretreatment with the selective β3-adrenoceptor antagonist SR59230 prevented all SR58611A-induced changes in cirrhotic rats. SR58611A concentration-dependently relaxed portal vein in cirrhotic rats to a significantly greater extent than in healthy rats; pretreatment with SR59230A completely prevented SR58611A-induced cirrhotic portal vein relaxation. Finally, β3-adrenoceptors were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats. CONCLUSIONS AND IMPLICATIONS β3-Adrenoceptors are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target. PMID:22708587

Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

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Jingchao Lu

2016-06-01

Full Text Available Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR rats 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 Amlodipine 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 blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

Diabetes and hypertension: experimental models for pharmacological studies

NARCIS (Netherlands)

van Zwieten, P. A.

1999-01-01

Since hypertensive and diabetes-mellitus frequently occur simultaneously there exists a requirement for animal models where both pathological entities are combined. The streptozotocin (STZ)-spontaneously hypertensive rat (STZ-SHR) and the obese Zucker rat are examples of animal models where

Effects of Lactobacillus plantarum TWK10-Fermented Soymilk on Deoxycorticosterone Acetate-Salt-Induced Hypertension and Associated Dementia in Rats

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Te-Hua Liu

2016-05-01

Full Text Available Oxidative stress resulting from excessive production of reactive oxygen species is the major mediator of neuronal cell degeneration observed in neurodegenerative diseases, such as Alzheimer’s disease (AD and vascular dementia (VaD. Additionally, hypertension has been shown to be a positive risk factor for VaD. Therefore, the objective of this study was to investigate the effects of Lactobacillus plantarum strain TWK10 (TWK10-fermented soymilk on the protection of PC-12 cells in H2O2-, oxygen-glucose deprivation (OGD- and deoxycorticosterone acetate (DOCA-salt-induced rat models of VaD. Notably, the viabilities of H2O2-treated PC-12 cells and OGD model were significantly increased by treatment with TWK10-fermented soymilk ethanol extract (p < 0.05. In addition, oral administration of TWK10-fermented soymilk extract in DOCA-salt hypertension-induced VaD rats resulted in a significant decrease in blood pressure (p < 0.05, which was regulated by inhibiting ACE activity and promoting NO production, in addition to decreased escape latency and increased target crossing (p < 0.05. In conclusion, these results demonstrated that TWK10-fermented soymilk extract could improve learning and memory in DOCA-salt hypertension-induced VaD rats by acting as a blood pressure-lowering and neuroprotective agent.

Electrocoagulation of the Locus coeruleus and the plasma catecholamine responses to immobilization stress in normotensive and hypertensive rats

International Nuclear Information System (INIS)

Dronjak, S.; Nikolic, J.; Varagic, V.M.

1998-01-01

The Locus coeruleus (LC), the largest noradrenergic nucleus in the brain, plays a major role in behavioral arousal in response to novel or stressful stimuli (Foote et al, 1983). An interesting feature of the LC is the degree of plasticity it displays in response to stress or drug treatment. For example, electrophysiological evidence suggests that sprouting of LC axons may occur following repeated stress (Sakaguchi and Nakamura, 1990). Stress increases LC firing rate and results in increased levels of noradrenaline (Glavin et al, 1983). High concentrations of noradrenergic neurons in LC indicated that this structure might have an integrative role in the blood pressure regulation. Spontaneously hypertensive rats (SHP) are widely used as a model of human essential hypertension. These animals exhibit enhanced sympathetic activity (Brody et al, 1980). It was therefore of interest to study the role of LC in normotensive and spontaneously hypertensive rats, and the effect of unilateral and bilateral electrocoagulation of the LC on the plasma concentration of noradrenaline and adrenaline during immobilization stress. (author)

Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

International Nuclear Information System (INIS)

El-Mas, Mahmoud M.; Helmy, Maged W.; Ali, Rabab M.; El-Gowelli, Hanan M.

2015-01-01

The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET A /ET B ) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg −1 day −1 , 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET A (increases) and ET B (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg −1 day −1 ), celecoxib (10 mg kg −1 day −1 ) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET A /ET B receptor expressions. Selective blockade of ET A receptors by atrasentan (5 mg kg −1 day −1 ) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET B receptor blocker, 0.1 mg kg −1 day −1 ) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET A downregulation and ET B upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats. • CSA increased and decreased renal ET A and ET B receptor expression, respectively. • CSA

HMGB1 promotes the development of pulmonary arterial hypertension in rats.

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Yukari Sadamura-Takenaka

Full Text Available Pulmonary arterial hypertension (PAH is characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. However, the molecular and cellular mechanisms driving inflammation have not been fully elucidated.To elucidate the roles of high mobility group box 1 protein (HMGB1, a ubiquitous DNA-binding protein with extracellular pro-inflammatory activity, in a rat model of PAH.Male Sprague-Dawley rats were administered monocrotaline (MCT. Concentrations of HMGB1 in bronchoalveolar lavage fluid (BALF and serum, and localization of HMGB1 in the lung were examined over time. The protective effects of anti-HMGB1 neutralizing antibody against MCT-induced PAH were tested.HMGB1 levels in BALF were elevated 1 week after MCT injection, and this elevation preceded increases of other pro-inflammatory cytokines, such as TNF-α, and the development of PAH. In contrast, serum HMGB1 levels were elevated 4 weeks after MCT injection, at which time the rats began to die. Immunohistochemical analyses indicated that HMGB1 was translocated to the extranuclear space in periarterial infiltrating cells, alveolar macrophages, and bronchial epithelial cells of MCT-injected rats. Anti-HMGB1 neutralizing antibody protected rats against MCT-induced lung inflammation, thickening of the pulmonary artery wall, and elevation of right ventricular systolic pressure, and significantly improved the survival of the MCT-induced PAH rats.Our results identify extracellular HMGB1 as a promoting factor for MCT-induced PAH. The blockade of HMGB1 activity improved survival of MCT-induced PAH rats, and thus might be a promising therapy for the treatment of PAH.

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

Science.gov (United States)

Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

2018-04-01

Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their

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

Repeated electroacupuncture attenuating of apelin expression and function in the rostral ventrolateral medulla in stress-induced hypertensive rats.

Science.gov (United States)

Zhang, Cheng-Rong; Xia, Chun-Mei; Jiang, Mei-Yan; Zhu, Min-Xia; Zhu, Ji-Min; Du, Dong-Shu; Liu, Min; Wang, Jin; Zhu, Da-Nian

2013-08-01

Studies have revealed that apelin is a novel multifunctional peptide implicated both in blood pressure (BP) regulation and cardiac function control. Evidence shows that apelin and its receptor (APJ) in the rostral ventrolateral medulla (RVLM) may play an important role in central BP regulation; however, its role is controversial and very few reports have shown the relationship between acupuncture and apelin. Our study aims to both investigate the apelinergic system role in stress-induced hypertension (SIH) and determine whether acupuncture therapy effects on hypertension involve the apelinergic system in the RVLM. We established the stress-induced hypertensive rat (SIHR) model using electric foot-shock stressors with noise interventions. The expression of both apelin and the APJ receptor in the RVLM neurons was examined by immunohistochemical staining and Western blots. The results showed apelin expression increased remarkably in SIHR while APJ receptor expression showed no significant difference between control and SIHR groups. Microinjection of apelin-13 into the RVLM of control rats or SIHR produced pressor and tachycardic effects. Furthermore, effects induced by apelin-13 in SIHR were significantly greater than those of control rats. In addition, repetitive electroacupuncture (EA) stimulation at the Zusanli (ST-36) acupoint attenuated hypertension and apelin expression in the RVLM in SIHR; it also attenuated the pressor effect elicited by exogenous apelin-13 microinjection in SIHR. The results suggest that augmented apelin in the RVLM was part of the manifestations of SIH; the antihypertensive effects of EA might be associated with the attenuation of apelin expression and function in the RVLM, which might be a novel role for EA in SIH setting. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-term inhibition of xanthine oxidase by febuxostat does not decrease blood pressure in deoxycorticosterone acetate (DOCA-salt hypertensive rats.

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Theodora Szasz

Full Text Available Xanthine oxidase and its products, uric acid and ROS, have been implicated in the pathogenesis of cardiovascular disease, such as hypertension. We have previously reported that allopurinol inhibition of XO does not alter the progression of deoxycorticosterone acetate (DOCA-salt hypertension in rats. However other researchers have observed a reduction in blood pressure after allopurinol treatment in the same model. To resolve this controversy, in this study we used the newer and more effective XO inhibitor febuxostat, and hypothesized that a more complete XO blockade might impair hypertension development and its end-organ consequences. We used DOCA-salt hypertensive rats and administered vehicle (salt water or febuxostat (orally, 5 mg/kg/day in salt water in a short-term "reversal" experiment (2 weeks of treatment 3 weeks after DOCA-salt beginning and a long-term "prevention" experiment (treatment throughout 4 weeks of DOCA-salt. We confirmed XO inhibition by febuxostat by measuring circulating and tissue levels of XO metabolites. We found an overall increase in hypoxanthine (XO substrate and decrease in uric acid (XO product levels following febuxostat treatment. However, despite a trend for reduced blood pressure in the last week of long-term febuxostat treatment, no statistically significant difference in hemodynamic parameters was observed in either study. Additionally, no change was observed in relative heart and kidney weight. Aortic media/lumen ratio was minimally improved by long-term febuxostat treatment. Additionally, febuxostat incubation in vitro did not modify contraction of aorta or vena cava to norepinephrine, angiotensin II or endothelin-1. We conclude that XO inhibition is insufficient to attenuate hypertension in the rat DOCA-salt model, although beneficial vascular effects are possible.

Long-term inhibition of xanthine oxidase by febuxostat does not decrease blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.

Science.gov (United States)

Szasz, Theodora; Davis, Robert Patrick; Garver, Hannah S; Burnett, Robert J; Fink, Gregory D; Watts, Stephanie W

2013-01-01

Xanthine oxidase and its products, uric acid and ROS, have been implicated in the pathogenesis of cardiovascular disease, such as hypertension. We have previously reported that allopurinol inhibition of XO does not alter the progression of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. However other researchers have observed a reduction in blood pressure after allopurinol treatment in the same model. To resolve this controversy, in this study we used the newer and more effective XO inhibitor febuxostat, and hypothesized that a more complete XO blockade might impair hypertension development and its end-organ consequences. We used DOCA-salt hypertensive rats and administered vehicle (salt water) or febuxostat (orally, 5 mg/kg/day in salt water) in a short-term "reversal" experiment (2 weeks of treatment 3 weeks after DOCA-salt beginning) and a long-term "prevention" experiment (treatment throughout 4 weeks of DOCA-salt). We confirmed XO inhibition by febuxostat by measuring circulating and tissue levels of XO metabolites. We found an overall increase in hypoxanthine (XO substrate) and decrease in uric acid (XO product) levels following febuxostat treatment. However, despite a trend for reduced blood pressure in the last week of long-term febuxostat treatment, no statistically significant difference in hemodynamic parameters was observed in either study. Additionally, no change was observed in relative heart and kidney weight. Aortic media/lumen ratio was minimally improved by long-term febuxostat treatment. Additionally, febuxostat incubation in vitro did not modify contraction of aorta or vena cava to norepinephrine, angiotensin II or endothelin-1. We conclude that XO inhibition is insufficient to attenuate hypertension in the rat DOCA-salt model, although beneficial vascular effects are possible.

Synchronization among Mechanisms of Renal Autoregulation is Reduced in Hypertensive Rats

DEFF Research Database (Denmark)

Sosnovtseva, Olga; Pavlov, A. N.; Mosekilde, Erik

2007-01-01

, and a slower (20-40 mHz) oscillation in tubuloglomerular feedback (TGF). These mechanisms interact; the TGF mode modulates both the amplitude and the frequency of the myogenic mode. Nephrons also communicate with each other using vascular signals triggered by membrane events in arteriolar smooth muscle cells...... in SHR is a state of partial synchronization with entrainment between neighboring nephrons for only one of the modes. Modulation of the myogenic mode by the TGF mode is much stronger in hypertensive than in normotensive rats. Synchronization among nephrons forms the basis for an integrated reaction...

Hypertension impairs postnatal vasculogenesis role of antihypertensive agents

NARCIS (Netherlands)

D. You (Dong); C. Cochain (Clément); C. Loinard (Céline); J. Vilar (Jose Manuel); B.M.E. Mees (Barend); M. Duriez (Micheline); B.I. Levy (Bernard); J.S. Silvestre (Jean Sebastien)

2008-01-01

textabstractWe analyzed the effect of hypertension on postischemic vasculogenesis. Ischemia was induced by right femoral artery ligature in Wistar Kyoto rats (WKY) or spontaneously hypertensive rats (SHR) treated with or without angiotensin-converting enzyme inhibitor (Perindopril, 0.76 mg/kg/d) and

Changes of imidazoline receptors in spontaneously hypertensive rats

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Mar, Guang-Yuan; Chou, Ming-Ting; Chung, Hsien-Hui; Chiu, Nien-Hua; Chen, Mei-Fen; Cheng, Juei-Tang

2013-01-01

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I1-receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (KATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I2-receptor, which is expressed more highly in SHRs. PMID:23176371

Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance.

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Potenza, Maria A; Marasciulo, Flora L; Tarquinio, Mariela; Quon, Michael J; Montagnani, Monica

2006-12-01

Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.

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

The Armed Forces Radiobiology Research Institute's linear accelerator was used to expose rats to high-energy electron radiation. The purpose of the study was to investigate 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 early transient incapacitation (ETI). Although male SHRs experienced a severe 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 examined. Male SHRs were significantly higher than normotensive controls on several blood chemistry determinations. Exposure to ionizing radiation tended to enhance these differences. These results could not be explained on the basis of radiogenic blood volume fluctuations

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.

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)

Autoradiographic study of the regional distribution of gastric blood flow in portal hypertensive rats

International Nuclear Information System (INIS)

Geraghty, J.G.; Angerson, W.J.; Carter, D.C.

1989-01-01

This study measures regional gastric blood flow in portal hypertensive rats at three separate periods after portal vein ligation using quantitative autoradiography with 14C-labeled iodoantipyrine. The level of corpus mucosal blood flow was significantly reduced in 3-day portal vein-ligated animals compared with sham-operated control animals (30.4 +/- 2.3 vs. 47.1 +/- 5.6 ml/100 g.min). There was no significant difference in corpus mucosal blood flow between portal vein-ligated and sham-operated animals at 7- and 28-day periods, although the level of perfusion was higher in the 28-day portal vein-ligated group. There was no significant difference in antral mucosal or muscle blood flow between portal hypertensive and control animals at any of the study periods. We conclude that the acute period after portal vein ligation is associated with a reduced corpus mucosal microcirculation but that this effect is not sustained in portal hypertensive animals studied at later intervals after portal vein ligation

PGC-1α mRNA Level and Oxidative Capacity of the Plantaris Muscle in Rats with Metabolic Syndrome, Hypertension, and Type 2 Diabetes

International Nuclear Information System (INIS)

Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Gu, Ning; Takeda, Isao; Ishioka, Noriaki; Tsuda, Kinsuke; Ishihara, Akihiko

2011-01-01

We examined the fiber profiles and the mRNA levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β) and of the PPARγ coactivator-1α (PGC-1α) in the plantaris muscles of 15-week-old control (WR), metabolic syndrome (CP), hypertensive (SHR), and type 2 diabetic (GK) rats. The deep regions in the muscles of SHR and GK rats exhibited lower percentages of high-oxidative type I and IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR and CP rats. The surface regions in the muscles of CP, SHR, and GK rats exhibited lower percentages of high-oxidative type IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR rats. The muscles of SHR and GK rats had lower oxidative enzyme activity compared with WR rats. The muscles of SHR rats had the lowest PPARδ/β mRNA level. In addition, the muscles of SHR and GK rats had lower PGC-1α mRNA level compared with WR and CP rats. We concluded that the plantaris muscles of rats with hypertension and type 2 diabetes have lower oxidative capacity, which is associated with the decreased level of PGC-1α mRNA

B-Type Natriuretic Peptide Deletion Leads to Progressive Hypertension, Associated Organ Damage, and Reduced Survival: Novel Model for Human Hypertension.

Science.gov (United States)

Holditch, Sara J; Schreiber, Claire A; Nini, Ryan; Tonne, Jason M; Peng, Kah-Whye; Geurts, Aron; Jacob, Howard J; Burnett, John C; Cataliotti, Alessandro; Ikeda, Yasuhiro

2015-07-01

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood. © 2015 American Heart Association, Inc.

Erythrocyte 22Na+ influx in hypertension

International Nuclear Information System (INIS)

Shalev, O.; Eaton, J.W.; Ben-Ishay, D.

1984-01-01

We assessed 22Na+ uptake by erythrocytes (RBC) from 38 individuals with essential hypertension and 37 healthy controls. All subjects were male, white, non-obese and with normal renal function, obviating sex, race, hormonal, ponderal and renal factors known to influence RBC Na+ handling. The mean +/- sem 22Na+ uptake of the patients was 284 +/- 16 mumole/liter RBC/hour while that of normal controls was 249 +/- 11 mumole/liter RBC/hour; although the difference reached borderline significance, individual values showed considerable overlap. Consequently, in our population, RBC 22Na+ uptake is not a reliable marker for essential hypertension. We believe that previous studies should be reassessed with regard to patients' characteristics and future studies employ rigorous criteria in selection of subjects

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.

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.

Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats.

Science.gov (United States)

Chelko, Stephen P; Schmiedt, Chad W; Lewis, Tristan H; Robertson, Tom P; Lewis, Stephen J

2014-01-01

This study compared the contractile responses elicited by angiotensin II (AII), arginine vasopressin (AVP), and 5-hydroxytryptamine (5-HT) in isolated occipital arteries (OAs) from sham-operated (SHAM) and 2-kidney, 1-clip (2K-1C) hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery) and distal segments (closer to the nodose ganglion) and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, heart rates, and plasma renin concentrations than SHAM rats. The contractile responses to AII were markedly diminished in both proximal and distal segments of OAs from 2K-1C rats as compared to those from SHAM rats. The responses elicited by AVP were substantially greater in distal than in proximal segments of OAs from SHAM rats and that AVP elicited similar responses in OA segments from 2K-1C rats. The responses elicited by 5-HT were similar in proximal and distal segments from SHAM and 2K-1C rats. These results demonstrate that continued exposure to circulating AII and AVP in 2K-1C rats reduces the contractile efficacy of AII but not AVP or 5-HT. The diminished responsiveness to AII may alter the physiological status of OAs in vivo.

Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats

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Stephen P. Chelko

2014-01-01

Full Text Available This study compared the contractile responses elicited by angiotensin II (AII, arginine vasopressin (AVP, and 5-hydroxytryptamine (5-HT in isolated occipital arteries (OAs from sham-operated (SHAM and 2-kidney, 1-clip (2K-1C hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery and distal segments (closer to the nodose ganglion and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, heart rates, and plasma renin concentrations than SHAM rats. The contractile responses to AII were markedly diminished in both proximal and distal segments of OAs from 2K-1C rats as compared to those from SHAM rats. The responses elicited by AVP were substantially greater in distal than in proximal segments of OAs from SHAM rats and that AVP elicited similar responses in OA segments from 2K-1C rats. The responses elicited by 5-HT were similar in proximal and distal segments from SHAM and 2K-1C rats. These results demonstrate that continued exposure to circulating AII and AVP in 2K-1C rats reduces the contractile efficacy of AII but not AVP or 5-HT. The diminished responsiveness to AII may alter the physiological status of OAs in vivo.

Propranolol modulates the collateral vascular responsiveness to vasopressin via a G(α)-mediated pathway in portal hypertensive rats.

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Lee, Jing-Yi; Huo, Teh-Ia; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Chang, Ching-Chih; Wang, Sun-Sang; Lee, Shou-Dong

2011-12-01

Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling

Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats

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M. Dolores Paredes

2018-04-01

Full Text Available Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks of the nitric oxide synthesis inhibitor, L-NAME. Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa or purified flavonoids (Apigenin and Diosmin for 6 weeks. Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and -independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

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Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

2014-12-01

Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. Copyright © 2014 the American Physiological Society.

Influence of mianserin on the activity of some hypotensive drugs in spontaneously hypertensive rats.

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Górska, Dorota; Andrzejczak, Dariusz

2003-01-01

Mianserin might be an alternative drug in patients with depression accompanied by hypertension because of its effectiveness and lack of side effects in the circulatory system. However, a few studies reported in literature show influence of the drug on blood pressure. We investigate interactions between mianserin and commonly used hypotensive drugs (propranolol, enalapril and prazosin) in spontaneously hypertensive rats (SHR). The experiments were performed in two experimental designs: a single administration of both mianserin and a hypotensive drug, and repeated administration of mianserin with a single administration of a hypotensive drug. Arterial blood pressure was measured by bloodless method with manometer made by LETICA. A single administration of mianserin caused a statistically significant decrease in systolic, diastolic and mean blood pressure in the 60th minute of observation and intensified hypotensive effect of prazosin. However, long-term administration of mianserin in SHR rats had no significant influence on arterial blood pressure. Chronic and single administration of mianserin with propranolol or enalapril did not influence the circulatory system. A long-term administration of mianserin intensified the hypotensive effect of prazosin. This interaction might suggest possibility of dangerous complications in the treatment of humans with this drug combination.

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:

Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension

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Silvia Llorens

2015-09-01

Full Text Available Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L. bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester or indomethacin (both 10−5 M, respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension.

Notch1 Mediates Preconditioning Protection Induced by GPER in Normotensive and Hypertensive Female Rat Hearts

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Carmine Rocca

2018-05-01

Full Text Available G protein-coupled estrogen receptor (GPER is an estrogen receptor expressed in the cardiovascular system. G1, a selective GPER ligand, exerts cardiovascular effects through activation of the PI3K-Akt pathway and Notch signaling in normotensive animals. Here, we investigated whether the G1/GPER interaction is involved in the limitation of infarct size, and improvement of post-ischemic contractile function in female spontaneous hypertensive rat (SHR hearts. In this model, we also studied Notch signaling and key components of survival pathway, namely PI3K-Akt, nitric oxide synthase (NOS and mitochondrial K+-ATP (MitoKATP channels. Rat hearts isolated from female SHR underwent 30 min of global, normothermic ischemia and 120 min of reperfusion. G1 (10 nM alone or specific inhibitors of GPER, PI3K/NOS and MitoKATP channels co-infused with G1, just before I/R, were studied. The involvement of Notch1 was studied by Western blotting. Infarct size and left ventricular pressure were measured. To confirm endothelial-independent G1-induced protection by Notch signaling, H9c2 cells were studied with specific inhibitor, N-[N-(3,5 difluorophenacetyl-L-alanyl]-S-phenylglycine t-butyl ester (DAPT, 5 μM, of this signaling. Using DAPT, we confirmed the involvement of G1/Notch signaling in limiting infarct size in heart of normotensive animals. In the hypertensive model, G1-induced reduction in infarct size and improvement of cardiac function were prevented by the inhibition of GPER, PI3K/NOS, and MitoKATP channels. The involvement of Notch was confirmed by western blot in the hypertensive model and by the specific inhibitor in the normotensive model and cardiac cell line. Our results suggest that GPERs play a pivotal role in mediating preconditioning cardioprotection in normotensive and hypertensive conditions. The G1-induced protection involves Notch1 and is able to activate the survival pathway in the presence of comorbidity. Several pathological conditions

Intestinal ion transport in rats with spontaneous arterial hypertension.

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Lübcke, R; Barbezat, G O

1988-08-01

1. Ion balance, intestinal ion transport in vivo with luminal Ringer, and direct voltage clamping in vivo with luminal Ringer and sodium-free choline-Ringer were studied in young (40 days old) and adult (120 days old) spontaneously hypertensive rats (SHR) and age-matched normotensive controls (Wistar-Kyoto rats, WKY). 2. Faecal sodium output was significantly higher in SHR compared with WKY in both young (+67%) and adult (+43%) rats. 3. Small-intestinal sodium absorption was equal in young SHR and WKY, but significantly greater net sodium absorption was found in the ileum of adult SHR. In contrast, net sodium absorption was reduced from the colon of both young and adult SHR. 4. In adult SHR, the colonic transepithelial short-circuit current (Isc) and the transepithelial potential difference (PD) were significantly higher, whereas the transepithelial membrane resistance (Rm) was significantly lower than in WKY. There was an identical drop in Isc in both strains when luminal sodium was replaced by choline. These data cannot be explained by increased electrogenic cation (sodium) absorption in the SHR, but would favour chloride secretion. 5. It is suggested that in SHR membrane electrolyte transport abnormalities may also be present in the epithelial cells of the small and large intestine, as have been demonstrated already in blood cells by several investigators. The SHR may become an interesting experimental animal model for the study of generalized ion transport disorders.

A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats

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Thaís de Oliveira Faria

Full Text Available Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR. Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS, phosphorylated endothelial nitric oxide synthase (p-eNOS1177 and inducible nitric oxide synthase (iNOS and to generate concentration-response curves to acetylcholine (ACh and to phenylephrine (PHE. The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME and indomethacin administration. The maximal response (Emax and the sensitivity (EC50 to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex rats (Emax= -80 ± 4.6%, p < 0.05 when compared to those of controls (Ct (Emax = -50 ± 6.8%. The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05 when compared to control conditions (120 ± 4.2%. This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05. Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

Biofeedback and Self-Regulation in Essential Hypertension.

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1977-09-20

SI n.c... ~ y aid ld.ruity by Mock numb.,) Biofeedback Operant condition ing Behav i oral factors in hypertension Re l axa ti on Meditation • 20...preliminary findings of a clini- cal study in which two types of biofeedback training were compared to a form of meditation in the treatment of borderline...behav ioral methods not involving the use of complex feedback techniques include progressive relaxation, medita- tion, yogic practices, autogenic

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

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R.C.A. Maia

2015-01-01

Full Text Available Exercise training (Ex has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP, reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g underwent surgery (2K1C or SHAM and were subsequently divided into a sedentary (SED group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks. Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS in the left ventricle, and increased the catalase (CAT activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

BLOCKADE OF ROSTRAL VENTROLATERAL MEDULLA (RVLM BOMBESIN RECEPTOR TYPE 1 DECREASES BLOOD PRESSURE AND SYMPATHETIC ACTIVITY IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

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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.

Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats.

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Zhou, Hong; Sun, Hai-jian; Chang, Jin-rui; Ding, Lei; Gao, Qing; Tang, Chao-shu; Zhu, Guo-qing; Zhou, Ye-bo

2014-10-01

Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension. Rats were subjected to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham-operation (Sham). Acute experiments were carried out four weeks later under anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical-vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25 pmol) caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52, non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or γ-amino butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve in the effect of IMD on CSAR in Sham and renovascular hypertensive rats. © 2014 by the Society for Experimental Biology and Medicine.

[Protective effect of arctigenin in GK rats combined with hypertension macroangiopathy].

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Feng, Qin; Sun, Bao-cun; Xia, Wen-kai

2015-03-01

To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin

Gallic acid attenuates calcium calmodulin-dependent kinase II-induced apoptosis in spontaneously hypertensive rats.

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Jin, Li; Piao, Zhe Hao; Liu, Chun Ping; Sun, Simei; Liu, Bin; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Kee, Hae Jin; Jeong, Myung Ho

2018-03-01

Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition-induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti-cancer, anti-calcification and anti-oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, β, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase-3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ-induced apoptosis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Arterial hypertension, microalbuminuria, and risk of ischemic heart disease

DEFF Research Database (Denmark)

Jensen, J S; Feldt-Rasmussen, B; Strandgaard, S

2000-01-01

Albumin excretion in urine is positively correlated with the presence of ischemic heart disease and atherosclerotic risk factors. We studied prospectively whether a slight increase of urinary albumin excretion, ie, microalbuminuria, adds to the increased risk of ischemic heart disease among...... hypertensive subjects. In 1983 and 1984, blood pressure, urinary albumin/creatinine concentration ratio, plasma total and HDL cholesterol levels, body mass index, and smoking status were obtained in a population-based sample of 2085 subjects, aged 30 to 60 years, who were free from ischemic heart disease......, diabetes mellitus, and renal or urinary tract disease. Untreated arterial hypertension or borderline hypertension was present in 204 subjects, who were followed until 1993 by the National Hospital and Death Certificate Registers with respect to development of ischemic heart disease. During 1978 person...

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

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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.

Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

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Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

2013-11-01

Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration

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Michał Biernacki

2018-05-01

In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted.

Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Chi, Liyi; Hu, Xiaojing; Zhang, Wentao; Bai, Tiao; Zhang, Linjing; Zeng, Hua; Guo, Ruirui; Zhang, Yanhai; Tian, Hongyan

2017-01-01

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. - Highlights: • Serum CTRP6 was significantly decreased in spontaneously hypertensive rats (SHRs). • CTRP6 positively regulated the activation of the ERK1/2 signaling pathway. • CTRP6 negatively regulates PPARγ mediated Angiotensin II (Ang

Study on inhibition of hypertension by low dose radiation

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Nakazono, Koichi; Watanabe, Nobukazu; Inoue, Masayasu.

1992-01-01

To elucidate the pathogenesis of hypertension, superoxide dismutase (HB-SOD) with high affinity for vascular endothelial cells was administered to spontaneously hypertensive rats (SHR). HB-SOD but not native SOD markedly decreased the blood pressure of SHR but not of control rats. The results suggest that regulation of superoxide and the related metabolites in and around vascular endothelial cells is important for controling blood pressure in hypertensive subjects. (author)

Arginase inhibition prevents the development of hypertension and improves insulin resistance in obese rats.

Science.gov (United States)

Peyton, Kelly J; Liu, Xiao-Ming; Shebib, Ahmad R; Johnson, Fruzsina K; Johnson, Robert A; Durante, William

2018-04-27

This study investigated the temporal activation of arginase in obese Zucker rats (ZR) and determined if arginase inhibition prevents the development of hypertension and improves insulin resistance in these animals. Arginase activity, plasma arginine and nitric oxide (NO) concentration, blood pressure, and insulin resistance were measured in lean and obese animals. There was a chronological increase in vascular and plasma arginase activity in obese ZR beginning at 8 weeks of age. The increase in arginase activity in obese animals was associated with a decrease in insulin sensitivity and circulating levels of arginine and NO. The rise in arginase activity also preceded the increase in blood pressure in obese ZR detected at 12 weeks of age. Chronic treatment of 8-week-old obese animals with an arginase inhibitor or L-arginine for 4 weeks prevented the development of hypertension and improved plasma concentrations of arginine and NO. Arginase inhibition also improved insulin sensitivity in obese ZR while L-arginine supplementation had no effect. In conclusion, arginase inhibition prevents the development of hypertension and improves insulin sensitivity while L-arginine administration only mitigates hypertension in obese animals. Arginase represents a promising therapeutic target in ameliorating obesity-associated vascular and metabolic dysfunction.

Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

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John P. Collister

2014-12-01

Full Text Available The brain senses circulating levels of angiotensin II (AngII via circumventricular organs, such as the subfornical organ (SFO, and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD, an intracellular superoxide (O2·− scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·− in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD or control vector (AdEmpty were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min for ten days. Rats over-expressing CuZnSOD (n = 7 in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9. These results support the hypothesis that production of O2·− in the MnPO contributes to the development of chronic AngII-dependent hypertension.

[Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

Science.gov (United States)

Liu, Wei; Zhu, Ling-Qun; Chen, Si-Si; Lu, Shu-Chao; Tang, Jie; Liu, Qing-Guo

2015-04-01

To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P arterial NOS and cGMP were markedly down-regulated (P arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P hypertensive effect in stress hypertension rats, which may be associated with its effects in raising blood Ach, and arterial NOS and cGMP levels.

Effects of hypertension and ovariectomy on rat hepatocytes. Are amlodipine and lacidipine protective? (A stereological and histological study).

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Dursun, Hakan; Albayrak, Fatih; Uyanik, Abdullah; Keleş, Nuri Osman; Beyzagül, Polat; Bayram, Ednan; Halici, Zekai; Altunkaynak, Zuhal Berrin; Süleyman, Halis; Okçu, Nihat; Ünal, Bünyamin

2010-12-01

Calcium channel blockers are increasingly used for the treatment of hypertension. Menopause and hypertension are both important risk factors for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of amlodipine and lacidipine in an ovariectomy-induced postmenopausal period model and a deoxycorticosterone acetate-salt-induced hypertensive model in rats. In this study, animals were divided into six groups as follows: control (Group 1), hypertension (Group 2), ovariectomy (Group 3), ovariectomy and hypertension (Group 4), ovariectomy, hypertension and amlodipine-treated (Group 5), and ovariectomy, hypertension and lacidipine-treated (Group 6). At the end of the experiment, the livers were removed and tissue samples were histologically and stereologically examined. The numerical densities of the hepatocytes according to group were 0.000422, 0.00329, 0.000272, 0.00259, 0.00374 and 0.000346 μm3, respectively. Significant differences were found between values of all groups (phypertension in Groups 5 and 6. Our experimental results show that both hypertension and the postmenopausal period have negative effects on the number of hepatocytes and histological structure of the liver. Both amlodipine and lacidipine appear to ameliorate the hypertension and/or postmenopausal period-related decrease in hepatocyte number. We thus suggest that lacidipine and particularly amlodipine have important protective and recovering effects on the liver.

Borderline Personality in the Medical Setting

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Sansone, Lori A.

2015-01-01

Objective: Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings—namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. Data Sources: We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet’s syndrome, somatic preoccupation, somatic. Study Selection: Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. Results: According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Conclusions: Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation. PMID:26644960

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

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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.

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

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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

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

Aims: 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. Methods: 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. Results: 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

Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats.

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Passos, Clévia Santos; Carvalho, Lucimeire Nova; Pontes, Roberto Braz; Campos, Ruy Ribeiro; Ikuta, Olinda; Boim, Mirian Aparecida

2012-02-01

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.

The benefits of endurance training in cardiomyocyte function in hypertensive rats are reversed within four weeks of detraining.

Science.gov (United States)

Carneiro-Júnior, Miguel Araujo; Quintão-Júnior, Judson Fonseca; Drummond, Lucas Rios; Lavorato, Victor Neiva; Drummond, Filipe Rios; da Cunha, Daise Nunes Queiroz; Amadeu, Marco Aurélio; Felix, Leonardo Bonato; de Oliveira, Edilamar Menezes; Cruz, Jader Santos; Prímola-Gomes, Thales Nicolau; Mill, José Geraldo; Natali, Antonio José

2013-04-01

The aim of the present study was to verify the effects of low-intensity endurance training and detraining on the mechanical and molecular properties of cardiomyocytes from spontaneously hypertensive rats (SHRs). Male SHRs and normotensive control Wistar rats at 16-weeks of age were randomly divided into eight groups of eight animals: NC8 and HC8 (normotensive and hypertensive control for 8weeks); NT8 and HT8 (normotensive and hypertensive trained at 50-60% of maximal exercise capacity for 8weeks); NC12 and HC12 (normotensive and hypertensive control for 12weeks); NDT and HDT (normotensive and hypertensive trained for 8weeks and detrained for 4weeks). The total exercise time until fatigue (TTF) was determined by a maximal exercise capacity test. Resting heart rate (RHR) and systolic arterial pressure (SAP) were measured. After the treatments, animals were killed by cervical dislocation and left ventricular myocytes were isolated by enzymatic dispersion. Isolated cells were used to determine intracellular global Ca(2+) ([Ca(2+)]i) transient and cardiomyocyte contractility (1Hz; ~25°C). [Ca(2+)]i regulatory proteins were measured by Western blot, and the markers of pathologic cardiac hypertrophy by quantitative real-time polymerase chain reaction (q-RT-PCR). Exercise training augmented the TTF (NC8, 11.4±1.5min vs. NT8, 22.5±1.4min; HC8, 11.7±1.4min vs. HT8, 24.5±1.3min; Pendurance training induces positive benefits to left ventricular myocyte mechanical and molecular properties, which are reversed within 4weeks of detraining. Copyright © 2013 Elsevier Ltd. All rights reserved.

Refeeding hypertension in dietary obesity

International Nuclear Information System (INIS)

Ernsberger, P.; Nelson, D.O.

1988-01-01

A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac β-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of [ 3 H]dihydroalpranolol; and (2) the decrease in heart rate as a result of β-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension

Noradrenaline concentration and turnover in nuclei of the hypothalamus and the medulla oblongata at two stages in the development of renal hypertension in the rat

NARCIS (Netherlands)

Wijnen, H.J.L.M.; Kloet, E.R. de; Versteeg, D.H.G.; Jong, Wybren de

1980-01-01

The noradrenaline concentration and the α-methyl-para-tyrosine (α-MPT)-induced disappearance of noradrenaline were determined in several nuclei of the hypothalamus and the medulla oblongata of renal hypertensive rats (two-kidney Goldblatt hypertension). A decreased α-MPT-induced disappearance of

Does Methylphenidate Affect Cystometric Parameters in Spontaneously Hypertensive Rats?

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Khae Hawn Kim

2015-06-01

Full Text Available Purpose: Methylphenidate (MPH is one of the most commonly prescribed psychostimulants for attention deficit hyperactivity disorder (ADHD. However, there is limited research on its effects on lower urinary tract function. This study investigated changes in cystometric parameters after intragastric administration of MPH in conscious spontaneously hypertensive rats (SHRs, an animal model of ADHD. Methods: Fourteen- to 16-week-old male SHRs (n=10, weighing between 280 and 315 g, were used. Three micturition cycles were recorded before administering MPH. One hour after each intragastric MPH injection, three cycles of cystometrogram were obtained in the awake condition. Various cystometric parameters were evaluated, including basal pressure (BP, maximal pressure (MP, threshold pressure (TP, bladder capacity (BC, micturition volume (MV, micturition interval (MI, and residual volume (RV. The data were analyzed using paired Student t-tests. Results: Five SHRs were each administered a dose of 3-mg/kg MPH, and the other five received a dose of 6-mg/kg MPH. BP and MP increased significantly in the rats that received the 3-mg/kg MPH injection, but not in those that received the 6-mg/kg injection. BC, MV, and MI significantly increased in the rats that received the 6-mg/kg MPH injection, but not in those that received the 3-mg/kg injection. There were no significant changes in TP after either injection. Conclusions: Significant increases in BC, MV, and MI after the 6-mg/kg MPH injection suggest that the peripheral and the central nervous systems may play important roles in bladder function in those receiving MPH for ADHD.

The Renal Protective Effect of Jiangya Tongluo Formula, through Regulation of Adrenomedullin and Angiotensin II, in Rats with Hypertensive Nephrosclerosis

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Lin Han

2015-01-01

Full Text Available We investigated the effect of Jiangya Tongluo (JYTL formula on renal function in rats with hypertensive nephrosclerosis. A total of 21 spontaneously hypertensive rats (SHRs were randomized into 3 groups: valsartan (10 mg/kg/d valsartan, JYTL (14.2 g/kg/d JYTL, and a model group (5 mL/kg/d distilled water; Wistar Kyoto rats comprised the control group (n = 7, 5 mL/kg/d distilled water. Treatments were administered by gavage every day for 8 weeks. Blood pressure, 24-h urine protein, pathological changes in the kidney, serum creatinine, and blood urea nitrogen (BUN levels were estimated. The contents of adrenomedullin (ADM and angiotensin II (Ang II in both the kidney and plasma were evaluated. JYTL lowered BP, 24-h urine protein, serum creatinine, and BUN. ADM content in kidneys increased and negatively correlated with BP, while Ang II decreased and negatively correlated with ADM, but there was no statistically significant difference of plasma ADM between the model and the treatment groups. Possibly, activated intrarenal renin-angiotensin system (RAS plays an important role in hypertensive nephrosclerosis and the protective function of ADM via local paracrine. JYTL may upregulate endogenous ADM level in the kidneys and antagonize Ang II during vascular injury by dilating renal blood vessels.

Omega-3 Fatty Acids Supplementation Differentially Modulates the SDF-1/CXCR-4 Cell Homing Axis in Hypertensive and Normotensive Rats.

Science.gov (United States)

Halmenschlager, Luiza; Lehnen, Alexandre Machado; Marcadenti, Aline; Markoski, Melissa Medeiros

2017-08-01

We assessed the effect of acute and chronic dietary supplementation of ω-3 on lipid metabolism and cardiac regeneration, through its influence on the Stromal Derived Factor-1 (SDF-1) and its receptor (CXCR4) axis in normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were allocated in eight groups (of eight animals each), which received daily orogastric administration of ω-3 (1 g) for 24 h, 72 h or 2 weeks. Blood samples were collected for the analysis of the lipid profile and SDF-1 systemic levels (ELISA). At the end of the treatment period, cardiac tissue was collected for CXCR4 expression analysis (Western blot). The use of ω-3 caused a reduction in total cholesterol levels ( p = 0.044), and acutely activated the SDF-1/CXCR4 axis in normotensive animals ( p = 0.037). In the presence of the ω-3, after 72 h, SDF-1 levels decreased in WKY and increased in SHR ( p = 0.017), and tissue expression of the receptor CXCR4 was higher in WKY than in SHR ( p = 0.001). The ω-3 fatty acid supplementation differentially modulates cell homing mediators in normotensive and hypertensive animals. While WKY rats respond acutely to omega-3 supplementation, showing increased release of SDF-1 and CXCR4, SHR exhibit a weaker, delayed response.

Tyrosine phosphorylation of Kv1.5 is upregulated in intrauterine growth retardation rats with exaggerated pulmonary hypertension

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L.C. Fu

2017-09-01

Full Text Available Intrauterine growth retardation (IUGR is associated with the development of adult-onset diseases, including pulmonary hypertension. However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular dysfunction later in life is not fully understood. Here, we investigated the role of tyrosine phosphorylation of voltage-gated potassium channel 1.5 (Kv1.5 in this prenatal event that results in exaggerated adult vascular dysfunction. A rat model of chronic hypoxia (2 weeks of hypoxia at 12 weeks old following IUGR was used to investigate the physiological and structural effect of intrauterine malnutrition on the pulmonary artery by evaluating pulmonary artery systolic pressure and vascular diameter in male rats. Kv1.5 expression and tyrosine phosphorylation in pulmonary artery smooth muscle cells (PASMCs were determined. We found that IUGR increased mean pulmonary artery pressure and resulted in thicker pulmonary artery smooth muscle layer in 14-week-old rats after 2 weeks of hypoxia, while no difference was observed in normoxia groups. In the PASMCs of IUGR-hypoxia rats, Kv1.5 mRNA and protein expression decreased while that of tyrosine-phosphorylated Kv1.5 significantly increased. These results demonstrate that IUGR leads to exaggerated chronic hypoxia pulmonary arterial hypertension (CH-PAH in association with decreased Kv1.5 expression in PASMCs. This phenomenon may be mediated by increased tyrosine phosphorylation of Kv1.5 in PASMCs and it provides new insight into the prevention and treatment of IUGR-related CH-PAH.

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

Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

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Gao, Jin-Hang; Wen, Shi-Lei; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Huang, Zhi-Yin; Liu, Zhang-Xu; Tang, Cheng-Wei

2013-01-01

Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, pportal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, pprotein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1α (HIF-1α), and c-fos were also down-regulated after celecoxib treatment. Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its modulation on VEGF/VEGFR-2 through the down-regulation of integrated signal pathways involving PGE2- HIF-1α- VEGF and p-ERK- c-fos- VEGFR-2.

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

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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.

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

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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.

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

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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.

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

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.

[Effects of qishenyiqi gutta pills on calcium/calmodulin dependent protein kinase II in rats with renal hypertension].

Science.gov (United States)

Zhang, Xiao-ying; Wei, Wan-lin; Shu, Chang-cheng; Zhang, Ling; Tian, Guo-xiang

2013-02-05

To explore the effects of qishenyiqi gutta pills on myocardial hypertrophy of left ventricle and calcium/calmodulin dependent protein kinase II (CAMK II) in rats with renal hypertension and elucidate its intervention mechanism for myocardial hypertrophy. A total of 50 Wistar rats were randomly divided into 5 groups of sham-operation, control, high-dose qishenyiqi gutta pills, low-dose qishenyiqi gutta pills and valsartan (n = 10 each). The rat model of myocardial hypertrophy with renal hypertension was established by the 2-kidney 1-clip (2K1C) method. The experimental animals were divided into control, high-dose, low-dose and valsartan groups. At Week 5 postoperation, valsartan group received an oral dose of valsartan (30 mg×kg(-1)×d(-1)), high-dose and low-dose groups took qishenyiqi gutta pills (250 and 125 mg×kg(-1)×d(-1)) while sham-operation and control groups had the same dose of normal saline solution. Tail arterial pressure was detected weekly and continued for 8 weeks. At the end of Week 12, the animals were sacrificed to harvest myocardial tissue of left ventricle for detecting left ventricular mass index (LVMI). The collagen volume fraction (CVF) of myocardium was examined by Van Gieson staining, the activities of superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA) and the expression of CAMK II was detected by immunohistochemistry and Western blot. (1) Blood pressures were significantly higher in high-dose, low-dose and control groups than those in sham-operation and valsartan groups ((167.66 ± 11.48), (166.72 ± 13.51), (174.34 ± 14.52) vs (119.57 ± 6.30), (131.80 ± 12.49) mm Hg, P pills may retard myocardial hypertrophy of left ventricle in rats with renal hypertension. And the mechanism is probably be correlated with its antioxidant activity and inhibited expression of myocardial CAMK II.

Central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature of renal hypertensive rats

NARCIS (Netherlands)

Nijkamp, F.P.; Ezer, Joseph; Jong, Wybren de

The central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature was studied in conscious renal hypertensive rats. Systemic administration of α-methyldopa decreased mean arterial blood pressure and body temperature and caused a short lasting increase in heart rate

Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

International Nuclear Information System (INIS)

Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

1986-01-01

The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

The CD147/MMP-2 signaling pathway may regulate early stage cardiac remodelling in spontaneously hypertensive rats.

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Li, Bowei; Zhou, Wanxing; Yang, Xiaorong; Zhou, Yuliang; Tan, Yongjing; Yuan, Congcong; Song, Yulan; Chen, Xiao; Zhang, Wei

2016-11-01

Previous studies have reported that decreased matrix metalloproteinase-2 (MMP-2) is associated with early stage (age 8-16 weeks) ventricular remodelling in spontaneously hypertensive rats (SHR). We hypothesized that inhibited CD147/MMP-2 signalling might down-regulate MMP-2 expression and augment remodelling in spontaneously hypertensive rats. Twenty-nine male SHR (8 weeks) were randomly assigned to SHR, CD147, and CD147+DOX groups. The control group included eight age-matched WKY rats. CD147 and CD147+DOX groups received recombinant human CD147 (600 ng/kg in 1.5 mL saline, weekly). The SHR and WKY groups received the vehicle. The CD147+DOX group also received doxycycline, an inhibitor of MMPs (daily, 30 mg/kg in 1.5 mL saline, iG). On day 56 echocardiography and left ventricular mass index (LVWI) measurements were collected and histological sections were stained for cell and collagen content. Myocardium MMP-2, TIMP-1, CD147, and collagens types I and III were estimated by western blot. CD147 and the ratio of MMP-2/TIMP-1 were lower in SHR than WKY rats (PCD147 rats showed CD147, MMP-2 and MMP-2/TIMP-1 were increased (PCD147 levels did not differ between CD147+DOX and CD147 groups, CVF, collagens type I and III and partial fiber breaks were more abundant in CD147+DOX (PCD147/MMP-2 pathway was associated with early stage cardiac remodelling, and CD147 supplementation may attenuate this response. © 2016 John Wiley & Sons Australia, Ltd.

Beta-adrenoceptor changes in hypertension: cause or consequence of the elevation in blood pressure?

NARCIS (Netherlands)

Kanczik, R.; Khamssi, M.; Michel, M. C.; Brodde, O. E.

1988-01-01

Cardiac, pulmonary and renal beta-adrenoceptor density and subtype distribution were measured by radioligand binding in three rat models of acquired hypertension. Dahl salt-sensitive (DS) rats on a high-sodium diet, renal hypertensive rats and DOCA-salt rats. The results were compared with

Pomegranate peel extract attenuates oxidative stress by decreasing coronary angiotensin-converting enzyme (ACE) activity in hypertensive female rats.

Science.gov (United States)

Dos Santos, Roger L; Dellacqua, Lais O; Delgado, Nathalie T B; Rouver, Wender N; Podratz, Priscila L; Lima, Leandro C F; Piccin, Mariela P C; Meyrelles, Silvana S; Mauad, Helder; Graceli, Jones B; Moyses, Margareth R

2016-01-01

Based on the antioxidant properties of pomegranate, this study was designed to investigate the effects of pomegranate peel extract on damage associated with hypertension and aging in a spontaneously hypertensive rat (SHR) model. The influence of pomegranate consumption was examined on systolic blood pressure (SBP), angiotensin-converting enzyme (ACE) coronary activity, oxidative stress, and vascular morphology. Four- or 28-wk-old SHR model rats were treated for 30 d, with terminal experimental animal age being 8 and 32 wk, respectively, with either pomegranate extract (SHR-PG) or filtered water (SHR). Data showed significant reduction in SBP and coronary ACE activity in both age groups. The levels of superoxide anion, a measure of oxidative stress, were significantly lower in animals in the SHR-PG group compared to SHR alone. Coronary morphology demonstrated total increases in vascular wall areas were in the SHR group, and pomegranate peel extract diminished this effect. Pomegranate peel extract consumption conferred protection against hypertension in the SHR model. This finding was demonstrated by marked reduction in coronary ACE activity, oxidative stress, and vascular remodelling. In addition, treatment was able to reduce SBP in both groups. Evidence indicates that the use of pomegranate peel extract may prove beneficial in alleviating coronary heart disease.

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

International Nuclear Information System (INIS)

Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

2006-01-01

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

Critical differences between two low protein diet protocols in the programming of hypertension in the rat.

Science.gov (United States)

Langley-Evans, S C

2000-01-01

Maternal nutrition has been identified as a factor determining fetal growth and risk of adult disease. In rats, the feeding of a low protein diet during pregnancy retards fetal growth and induces hypertension in the resulting offspring. Rat models of low protein feeding have been extensively used to study the mechanisms that may link maternal nutrition with impaired fetal growth and later cardiovascular disease and diabetes. Low protein diets of differing composition used in different laboratories have yielded inconsistent data on the relationship between maternal protein intake and offsprings' blood pressure. Two separate low protein diet protocols were compared in terms of their ability to programme hypertension during fetal life. Pregnant rats were assigned to receive one of four diets. Two diets were obtained from a commercial supplier and provided casein at 22 or 9% by weight (H22, control; H9, low protein). The other two diets, manufactured in our own facility, provided 18% casein (S18, control) or 9% casein (S9, low protein) by weight. The diets differed principally in their overall fat content, fatty acid composition, methionine content and the source of carbohydrate. Feeding of the experimental diets commenced on the first day of pregnancy and continued until the rats delivered their litters. Following weaning all the offspring had blood pressure determined on a single occasion. Both low protein diets reduced maternal weight gain relative to their corresponding control diets. Despite this litter sizes were unaffected by the dietary protocols. Both low protein diets reduced birthweights of the pups. Systolic blood pressure was significantly elevated in the offspring of rats fed a low protein S9 diet relative to all other groups (P work that differing low protein diet manipulations in rat pregnancy elicit different programming effects upon the developing cardiovasculature. The balance of protein and other nutrients may be a critical determinant of the long

WATER EXTRACT OF PURPLE SWEET POTATO TUBERS REDUCES BLOOD PRESSURE 0F HYPERTENSIVE RATS INDUCED BY NaCl

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I MADE JAWI

2013-04-01

Full Text Available Compliance of hypertensive patients to take medication is one of many determinant factors to achieve successful treatment. Side effects and the expensive price of drugs are the causes of the incompliance of patients taking the medication. Utilization of herbal medicine is a new hope to resolve the issue. Purple sweet potato tuber is a plant part that expected has beneficial effect in lowering blood pressure because it contains anthocyanins which are antioxidants and can preserve endothelial function. To prove these hypothesis, a study was conducted with randomized control group pre and post-test design. The  study was done on 20 adult male Wistar rats that were divided into two groups of 10 rats.  Both groups of rats were made hypertensive by administering high doses of NaCl. Control group of rats given only NaCl alone for 14 days. Treatment group were given NaCl and water extract of purple sweet potato tuber with a dose of 4 cc per day for 14 days. Before treatment and during treatment, blood pressure were taken everyday with special sphygmomanometer. The results indicate a significant difference in blood pressure between the control group with treatment (P = 0.0001. In the treatment group, it was observed that there was a significant decrease in blood pressure compared to the control group (P=0.0001. From the results of this study, it can be concluded that administration of purple sweet potato tuber water extract may lower high blood pressure of rats induced by NaCl.

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

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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

The Effect of Physical Resistance Training on Baroreflex Sensitivity of Hypertensive Rats

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Moisés Felipe Pereira Gomes

Full Text Available Abstract Background: Baroreceptors act as regulators of blood pressure (BP; however, its sensitivity is impaired in hypertensive patients. Among the recommendations for BP reduction, exercise training has become an important adjuvant therapy in this population. However, there are many doubts about the effects of resistance exercise training in this population. Objective: To evaluate the effect of resistance exercise training on BP and baroreceptor sensitivity in spontaneously hypertensive rats (SHR. Method: Rats SHR (n = 16 and Wistar (n = 16 at 8 weeks of age, at the beginning of the experiment, were randomly divided into 4 groups: sedentary control (CS, n = 8; trained control (CT, n = 8; sedentary SHR (HS, n = 8 and trained SHR (HT, n = 8. Resistance exercise training was performed in a stairmaster-type equipment (1.1 × 0.18 m, 2 cm between the steps, 80° incline with weights attached to their tails, (5 days/week, 8 weeks. Baroreceptor reflex control of heart rate (HR was tested by loading/unloading of baroreceptors with phenylephrine and sodium nitroprusside. Results: Resistance exercise training increased the soleus muscle mass in SHR when compared to HS (HS 0.027 ± 0.002 g/mm and HT 0.056 ± 0.003 g/mm. Resistance exercise training did not alter BP. On the other hand, in relation to baroreflex sensitivity, bradycardic response was improved in the TH group when compared to HS (HS -1.3 ± 0.1 bpm/mmHg and HT -2.6 ± 0.2 bpm/mmHg although tachycardia response was not altered by resistance exercise (CS -3.3 ± 0.2 bpm/mmHg, CT -3.3 ± 0.1 bpm/mmHg, HS -1.47 ± 0.06 bpm/mmHg and HT -1.6 ± 0.1 bpm/mmHg. Conclusion: Resistance exercise training was able to promote improvements on baroreflex sensitivity of SHR rats, through the improvement of bradycardic response, despite not having reduced BP.

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

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

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

OpenAIRE

Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David; Jalili, Thunder

2013-01-01

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-...

Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney.

Science.gov (United States)

Maji, Uttam Kumar; Jana, Pradipta; Chatterjee, Mitali; Karmakar, Sanmay; Saha, Arup; Ghosh, Tamal Kanti

2018-03-01

Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent. In our study, acetyl salicylic acid (aspirin), a well-known activator of the endothelial nitric oxide synthase (eNOS) induced r-cortexin synthesis. The hypertensive rat model was prepared by injecting deoxy corticosterone acetate (DOCA). Synthesis of r-cortexin was measured by the anti-r-cortexin antibody which was raised in adult white Wister albino rat model. NO level was determined by using methemoglobin method and later confirmed by chemiluminescence method. Change in blood pressure was determined indirectly by using NIBP monitoring system. Aspirin increased the r-cortexin expression from 64.36 ± 12.6 nM to 216.7 ± 21.31 nM in DOCA induced hypertensive rats. The mechanism was proved with the findings of increased level of NO from 0.4 to 1.9 µM. The DOCA induced blood pressure was also decreased from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg in case of systolic blood pressure and in case of diastolic pressure from 110.41 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg that are quite approximate. So, from this study it has been found that aspirin induces the r-cortexin synthesis in kidney cortex through the activation of eNOS in DOCA induced hypertensive rats.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

Science.gov (United States)

Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

2017-12-11

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

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A. Caires

2017-12-01

Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Investigating the Correlation of Alexithymia in People with Borderline Tendencies with Impulsivity, Self-Harm and Borderline Personality Traits

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Ahmad Mirgol

2018-03-01

Full Text Available Background and Objectives: The borderline personality disorder includes a cluster of syndromes and symptoms characterized by instable and impulsive behaviors. The aim of the present study was to investigate the correlation of alexithymia in people with borderline tendencies with impulsivity, self-harm and borderline personality traits. Material and Methods: In a descriptive-correlational and cross sectional research approach, 350 students from Tabriz University were selected using random cluster sampling. From this sample, 115 people with a borderline score higher than the cut-off point were chosen and labeled as people with borderline tendencies. Toronto Alexithymia Scale-20, STB, and SHI questionnaires were used to collect data. The data were analyzed using Pearson product-moment correlation and simultaneous multiple regression by SPSS software v.21. Results: The findings indicated that alexithymia has a positive and meaningful relationship with borderline personality traits (r=0.36, p Conclusion: Based on these findings, we can conclude that alexithymia and problems in identifying feelings are the main determinants of borderline personality traits and impulsivity. Also, alexithymia and problems in identifying feelings and problems in describing feelings subscales are the main determinants of self-harm.

Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.

Science.gov (United States)

Sakamoto, Masaharu; Nakamura, Toru; Torimura, Takuji; Iwamoto, Hideki; Masuda, Hiroshi; Koga, Hironori; Abe, Mitsuhiko; Hashimoto, Osamu; Ueno, Takato; Sata, Michio

2013-01-01

In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

Science.gov (United States)

Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

1998-01-01

We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

Heat stress proteins in hypertension

International Nuclear Information System (INIS)

Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

1986-01-01

It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46 0 C during 5 min in a hot water bath. The cells were then labeled with ( 75 Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

Science.gov (United States)

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

Effect of Rho kinase inhibitor fasudil on the expression ET-1 and NO in rats with hypoxic pulmonary hypertension.

Science.gov (United States)

Sun, Xing-Zhen; Li, Shu-Yan; Tian, Xiang-Yang; Hong, Ze; Li, Jia-Xin

2018-04-12

This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups. MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced. Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.

MRI appearances of borderline ovarian tumours

Energy Technology Data Exchange (ETDEWEB)

Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

2009-04-15

This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

Science.gov (United States)

Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

2003-09-01

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

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

Directory of Open Access Journals (Sweden)

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.

Genome-wide analyses of borderline personality features

NARCIS (Netherlands)

Lubke, G.H.; Laurin, C.; Amin, N.; Hottenga, J.J.; Willemsen, G.; Grootheest, G.; Abdellaoui, A.; Karssen, L.C.; Oostra, B.A.; van Duijn, C.M.; Penninx, B.W.J.H.; Boomsma, D.I.

2014-01-01

The heritability of borderline personality (BP) features has been established in multiple twin and family studies. Using data from the borderline subscale of the Personality Assessment Inventory Borderline Features Scale (PAI-BOR) collected in two Dutch cohorts (N=7125), the Netherlands Twin

Transtorno borderline: história e atualidade

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Paulo Dalgalarrondo

Full Text Available No presente trabalho é feita uma revisão histórica e psicopatológica do distúrbio borderline. O autor sugere que a categoria clínica introduzida por Kahlbaum, em 1890, “heiboidophenie”, pode ser considerada como um protoconceito na origem do conceito de transtorno borderline. No final dos anos 70 e 80, sob a influência do DMS-III, a esquizofrenia latente ou borderline se transformava em dois subtipos de transtorno de personalidade: borderline e esquizotípico. Alguns aspectos psicopatológicos do Transtorno de Personalidade Borderline são revistos, com especial ênfase sobre os sintomas afetivos e as alterações no plano das relações interpessoais.

Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

Science.gov (United States)

Agafonova, I G; Bogdanovich, R N; Kolosova, N G

2015-12-01

Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration.

Powerful vascular protection by combining cilnidipine with valsartan in stroke-prone, spontaneously hypertensive rats

OpenAIRE

Takai, Shinji; Jin, Denan; Aritomi, Shizuka; Niinuma, Kazumi; Miyazaki, Mizuo

2012-01-01

Cilnidipine is an L- and N-type calcium channel blocker (CCB), and amlodipine is an L-type CCB. Valsartan (10?mg?kg?1), valsartan (10?mg?kg?1) and amlodipine (1?mg kg?1), and valsartan (10?mg?kg?1) and cilnidipine (1?mg?kg?1) were administered once daily for 2 weeks to stroke-prone, spontaneously hypertensive rats (SHR-SPs). Blood pressure was significantly reduced by valsartan, and it was further reduced by the combination therapies. Vascular endothelial dysfunction was significantly attenua...

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

Vascular Remodeling in Experimental Hypertension

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Norma R. Risler

2005-01-01

Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

Opposite effects of training in rats with stable and progressive pulmonary hypertension.

Science.gov (United States)

Handoko, M L; de Man, F S; Happé, C M; Schalij, I; Musters, R J P; Westerhof, N; Postmus, P E; Paulus, W J; van der Laarse, W J; Vonk-Noordegraaf, A

2009-07-07

Exercise training in pulmonary arterial hypertension (PH) is a promising adjunct to medical treatment. However, it is still unclear whether training is beneficial for all PH patients. We hypothesized that right ventricular adaptation plays a pivotal role in the response to training. Two different dosages of monocrotaline were used in rats to model stable PH with preserved cardiac output and progressive PH developing right heart failure. Two weeks after injection, PH was confirmed by echocardiography, and treadmill training was initiated. Rats were trained for 4 weeks unless manifest right heart failure developed earlier. At the end of the study protocol, all rats were functionally assessed by endurance testing, echocardiography, and invasive pressure measurements. Lungs and hearts were further analyzed in quantitative histomorphologic analyses. In stable PH, exercise training was well tolerated and markedly increased exercise endurance (from 25+/-3.9 to 62+/-3.9 minutes; Ptraining worsened survival (hazard ratio, 2.7; 95% confidence interval, 1.1 to 14.2) and increased pulmonary vascular remodeling. In addition, training induced widespread leukocyte infiltration into the right ventricle (from 135+/-14 to 276+/-18 leukocytes per 1 mm(2); Ptraining was found to be beneficial in stable PH but detrimental in progressive PH. Future studies are necessary to address the clinical implications of our findings.

Relationship between brain atrophy estimated by a longitudinal computed tomography study and blood pressure control in patients with essential hypertension

Energy Technology Data Exchange (ETDEWEB)

Yamano, Shigeru; Sawai, Fuyuki; Yamamoto, Yuta [Nara Medical Univ., Kashihara (Japan)] [and others

1999-01-01

To evaluate the relationship between blood pressure control and the progression of brain atrophy in the elderly, patients with essential hypertension and brain atrophy were longitudinally evaluated using computerized tomography (CT). The study evaluated 48 patients with essential hypertension aged 46-78 years, and 30 sex- and age-matched normotensive control subjects. The extent of brain atrophy as determined by caudate head index (CHI), the inverse cella media index (iCMI), and Evans` ratio (ER) was estimated twice at an interval of 5-9 years (mean, 6.9 years). The mean annual increases in CHI ({Delta}CHI), iCMI ({Delta}iCMI), and ER ({Delta}ER) were evaluated. Mean blood volume in the common carotid artery (BF) and the decrease in BF per year ({Delta}BF) were also determined. The {Delta}CHI, {Delta}iCMI, and {Delta}ER increased with age in the hypertensive subjects as well as the control group across all age groups evaluated. The {Delta}CHI, {Delta}iCMI, and {Delta}ER were significantly greater in the patients with essential hypertension in their 50s as compared with the controls. In patients with essential hypertension aged 65 years or older, the {Delta}CHI, {Delta}iCMI, and {Delta}ER were significantly lower in the group in whom the blood pressure was controlled within the range of borderline hypertension than the groups in which it was controlled in the range of normal or mild hypertension. In the younger patients under the age of 65 with essential hypertension, blood pressure control did not affect the {Delta}CHI, {Delta}iCMI, and {Delta}ER. The {Delta}CHI, {Delta}iCMI, and {Delta}ER were significantly correlated with {Delta}BF in both groups. These findings indicate that control of systolic blood pressure within the range of borderline hypertension may delay the progression of brain atrophy in elderly patients with essential hypertension. (author)

Relationship between brain atrophy estimated by a longitudinal computed tomography study and blood pressure control in patients with essential hypertension

International Nuclear Information System (INIS)

Yamano, Shigeru; Sawai, Fuyuki; Yamamoto, Yuta

1999-01-01

To evaluate the relationship between blood pressure control and the progression of brain atrophy in the elderly, patients with essential hypertension and brain atrophy were longitudinally evaluated using computerized tomography (CT). The study evaluated 48 patients with essential hypertension aged 46-78 years, and 30 sex- and age-matched normotensive control subjects. The extent of brain atrophy as determined by caudate head index (CHI), the inverse cella media index (iCMI), and Evans' ratio (ER) was estimated twice at an interval of 5-9 years (mean, 6.9 years). The mean annual increases in CHI (ΔCHI), iCMI (ΔiCMI), and ER (ΔER) were evaluated. Mean blood volume in the common carotid artery (BF) and the decrease in BF per year (ΔBF) were also determined. The ΔCHI, ΔiCMI, and ΔER increased with age in the hypertensive subjects as well as the control group across all age groups evaluated. The ΔCHI, ΔiCMI, and ΔER were significantly greater in the patients with essential hypertension in their 50s as compared with the controls. In patients with essential hypertension aged 65 years or older, the ΔCHI, ΔiCMI, and ΔER were significantly lower in the group in whom the blood pressure was controlled within the range of borderline hypertension than the groups in which it was controlled in the range of normal or mild hypertension. In the younger patients under the age of 65 with essential hypertension, blood pressure control did not affect the ΔCHI, ΔiCMI, and ΔER. The ΔCHI, ΔiCMI, and ΔER were significantly correlated with ΔBF in both groups. These findings indicate that control of systolic blood pressure within the range of borderline hypertension may delay the progression of brain atrophy in elderly patients with essential hypertension. (author)

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

DEFF Research Database (Denmark)

Gall, M A; Rossing, P; Skøtt, P

1992-01-01

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

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

Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

Directory of Open Access Journals (Sweden)

Jin-Hang Gao

Full Text Available BACKGROUND: Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2 in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVE: To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA. 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF, VEGF receptor-2 (VEGFR-2 and related signal molecules were quantitated. RESULTS: Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2, phosphorylated extracellular signal-regulated kinase (p-ERK, hypoxia-inducible factor-1α (HIF-1α, and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONS: Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its

Flow- and acetylcholine-induced dilation in small arteries from rats with renovascular hypertension - effect of tempol treatment

DEFF Research Database (Denmark)

Christensen, Frank Holden; Stankevicius, Edgaras; Hansen, Thomas

2007-01-01

-treated animals, while only the relaxation was improved by the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In conclusion renovascular hypertension selectively inhibits flow-induced NO-mediated vasodilatation, while EDHF-type vasodilatation remains unaffected, suggesting that high blood pressure leads...... blood pressure and tempol treatment. Simultaneous measurements of NO-concentration and relaxation were performed in isolated coronary arteries from the same animals. As compared to vehicle-treated rats, both acetylcholine-induced relaxation and NO-concentration increased in arteries from tempol......-induced dilatation remained normal. Measured by dihydroethidium staining there was an increased amount of superoxide in arteries from vehicle-treated rats, but not from tempol-treated rats. Expression by immunoblotting of endothelial NO synthase and the NAD(P)H oxidase subunit p47phox remained unaffected by high...

Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats.

Science.gov (United States)

Dai, S-Y; Fan, J; Shen, Y; He, J-J; Peng, W

2016-05-01

Endoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension. Male, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin. ANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females. The results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Azerbaijan-Russia Borderline Security

Directory of Open Access Journals (Sweden)

Ekaterina V. Arkhipova

2017-03-01

Full Text Available The Azerbaijan-Russia borderline mainly goes by the Caucasian mountain range and close to the Samur riverbed. Main border posts are situated close to the Caspian seashore while the locals living in the Upper Dagestan area have difficulties with crossing borderline. The locals are represented by the so called “divided peoples” whose living area was divided with the state border after 1991. The former inner borders ignored ethnic areas but now they became the lines crossing the ethnic groups of Legins, Avars, Tzakhurs and Rutuls. Certainly, those peoples are interested in specific rules for crossing the border. At the same time, their areas have not got the equipped border offices and they have to spend a lot of time and money for travelling to the neighboring districts via Baku or Vladikavkaz. Such problems arouse the radical demands among locals. The Lezgin movement for an independent Lezgistan is the most famous among them. Its supporters were involved in a terrorist attack in Baku in 1990-s and now they collect files about any problems connected with border issues, including the results of a demarcation process. They attract attention to the facts of all assignments made by Russian representatives. The activity of other ethnic groups was comparatively lower and they could make an agreement with local authorities about division of powers. Obviously, any solution about development of the border infrastructure may stabilize the separatism activity in the area. The author determines the key challenges and threats to cross-border security at Azerbaijan-Russia borderline on the basis of analysis of Federal and regional media, declarations made by representatives of the local and borderline authorities, as well as online activities of national movements. The author reveals the infrastructure factors of ensuring cross-border activity, social and economic conditions of borderline districts development. The suggestion is made on the need to develop

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

Beneficial Effect of Ocimum sanctum (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

Science.gov (United States)

Meghwani, Himanshu; Prabhakar, Pankaj; Mohammed, Soheb A; Dua, Pamila; Seth, Sandeep; Hote, Milind P; Banerjee, Sanjay K; Arava, Sudheer; Ray, Ruma; Maulik, Subir Kumar

2018-04-17

The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective. Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue. OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT. The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil.

[The influnence of dachengqi tang on acute lung injury and intra abdominal hypertension in rats with acute pancreatitis].

Science.gov (United States)

Wan, Mei-Hua; Li, Juan; Tang, Wen-Fu; Gong, Han-Lin; Chen, Guang-Yuan; Xue, Ping; Zhao, Xian-Lin; Xia, Qing

2011-09-01

To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P 0.05). Only two rats in the ANP group died. DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".

Baroreflex control of sympathetic activity in experimental hypertension

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M.C.C. Irigoyen

1998-09-01

Full Text Available The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100% was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

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

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

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

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Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

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

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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.

The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁ and hypertension (S1P₃ in rat.

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Ryan M Fryer

Full Text Available Sphingosine-1-phospate (S1P and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X receptor agonist produces modest hypertension in patients (2-3 mmHg in 1-yr trial as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension, and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P₁,₅ agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min elicited acute bradycardia in anesthetized rats demonstrating an S1P₁ mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls, BAF312 (0.3, 3.0, 30.0 mg/kg/d had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P₃ receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P₁ receptors mediate bradycardia while hypertension is mediated by S1P₃ receptor activation.

Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

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Xu Xue-Feng

2013-02-01

Full Text Available Abstract Background Accumulating evidence reveals that intrauterine growth retardation (IUGR can cause varying degrees of pulmonary arterial hypertension (PAH later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. Methods The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC were isolated from the rat lungs by magnetic-activated cell sorting (MACS. We investigated epigenetic regulation of the endothelin-1 (ET-1 gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. Results The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. Conclusions These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats.

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Yao, Jian; Qin, Xiaotong; Zhu, Jianhua; Sheng, Hongzhuan

2016-01-01

It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling. © 2015 S. Karger AG, Basel.

[The effect of calcitonin gene-related peptide on collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary arterial hypertension].

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Li, Xian-Wei; Du, Jie; Li, Yuan-Jian

2013-03-01

To observe the effect of calcitonin gene-related peptide (CGRP) on pulmonary vascular collagen accumulation in hypoxia rats in order to study the effect of CGRP on hypoxic pulmonary vascular structural remodeling and its possible mechanism. Rats were acclimated for 1 week, and then were randomly divided into three groups: normoxia group, hypoxia group, and hypoxia plus capsaicin group. Pulmonary arterial hypertension was induced by hypoxia in rats. Hypoxia plus capsaicin group, rats were given capsaicin (50 mg/(kg x d), s.c) 4 days before hypoxia to deplete endogenous CGRP. Hypoxia (3% O2) stimulated proliferation of pulmonary arterial smooth muscle cells (PASMCs) and proliferation was measured by BrdU marking. The expression levels of CGRP, phosphorylated ERK1/2 (p-ERK1/ 2), collagen I and collagen III were detected by real-time PCR or Western blot. Right ventricle systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) of pulmonary arterial hypertension (PAH) rats induced by hypoxia were higher than those of normoxia rats. By HE and Masson staining, it was demonstrated that hypoxia also significantly induced hypertrophy of pulmonary arteries and increased level of collagen accumulation. Hypoxia dramatically decreased the CGRP level and increased the expression of p-ERK1/2, collagen I, collagen III in pulmonary arteries. All these effects of hypoxia were further aggravated by pre-treatment of rats with capsaicin. CGRP concentration-dependently inhibited hypoxia-induced proliferation of PASMCs, markedly decreased the expression of p-ERK1/2, collagen I and collagen III. All these effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that CGRP might inhibit hypoxia-induced PAH and pulmonary vascular remodeling, through inhibiting phosphorylation of ERK1/2 and alleviating the collagen accumulation of pulmonary arteries.

Neurochemical alterations associated with borderline personality disorder.

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Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

2015-01-01

In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder. © 2015, The Author(s).

Developmental aspects of borderline personality disorder.

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Reich, D B; Zanarini, M C

2001-01-01

This study examined whether patients with borderline personality disorder and controls with other personality disorders remember their childhoods differently with respect to separation difficulties, evocative memory, temperamental factors such as frustration tolerance and mood reactivity, and onset of symptoms. Two hundred and ninety patients with borderline personality disorder and 72 with other personality disorders were assessed using an instrument to rate memories of separation difficulties, temperamental problems, and onset of symptoms before age 18. Patients with borderline personality disorder remembered more difficulties with separation between ages 6 and 17 years, more mood reactivity and poorer frustration tolerance between ages 6 and 17, and the onset of more symptoms (most prominently sadness, depression, anxiety, and suicidality) before age 18 than did patients with other personality disorders. The groups did not differ in reports of evocative memory before age 18. These results indicate that many of the features of adult patients with borderline personality disorder may initially appear during childhood and adolescence and that these features may be used to differentiate borderline from other personality disorders.

The role of vascular protein and renin in chronic two-kidney, one clip Goldblatt hypertension

International Nuclear Information System (INIS)

Nakada, T.; Yamori, Y.

1982-01-01

Chronic hypertension was induced in rats by application of a clip for 17 or 20 weeks to the unilateral renal artery and leaving the contrarenal vessel intact. Some of the rats received antihypertensive treatment with phenoxybenzamine (POB). 3 H-proline was injected into all rats in the 17th experimental week to observe the in vivo incorporation rates of 3 H-proline into vascular non-collagenous protein and vascular collagen. Plasma renin activity (PRA) of decapitated rats was assayed in the terminal stage of the experiment. Significant differences were noted between 2K-1C hypertensive rats and sham-operated normotensive rats, the former rats having significantly higher incorporation rates of 3 H-proline into non-collagenous protein and collagen of testicular or mesenteric artery. These results indicate that increased synthesis of vascular non-collagenous protein as well as collagen, especially of small arteries, plays a major role for the pathogenesis of chronic hypertension in 2K-1C rats, and renin does not contribute to elevation of the blood pressure in the maintenance phase of this type of experimental hypertension

Effect of Clonidine (an Antihypertensive Drug Treatment on Oxidative Stress Markers in the Heart of Spontaneously Hypertensive Rats

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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.

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model

International Nuclear Information System (INIS)

Mochizuki, Takafumi; Tsukamoto, Eriko; Ono, Tomohide

1997-01-01

Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with 125 I-BMIPP, a branched fatty acid analog. SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of 125 I-BMIPP and 201 Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition, 125 I-BMIPP uptake was corrected by 201 Tl uptake (B/T). The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p 125 I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373±0.212, 18 weeks; 1.380±0.047: mean±SE, p 125 I-BMIPP and 201 Tl. (author)

Altered regulation of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

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Jung, Ji Yong; Lee, Jay Wook; Kim, Sejoong; Jung, Eun Sook; Jang, Hye Ryoun; Han, Jin Suk; Joo, Kwon Wook

2009-12-01

Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na(+)/K(+)/2Cl(-) cotransporter (NKCC2) and Na(+)/Cl(-) cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-α and ENaC-β in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-α and ENaC-β were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells

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Haefliger J.-A.

2000-01-01

Full Text Available Connexin43 (Cx43, the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension on the expression of Cx43 in aorta and heart in three different models of experimental hypertension. Rats were made hypertensive either by clipping one renal artery (two kidney, one-clip renal (2K,1C model by administration of deoxycorticosterone and salt (DOCA-salt model or by inhibiting nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME model. After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respective controls. The same 2K,1C and DOCA-salt hypertensive animals expressed twice more Cx43 in aorta, and the 2K,1C rats showed an increase in arterial distensibility. In contrast, the aortae of L-NAME hypertensive rats were characterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was more phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or control rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell communication mediated by Cx43 channels may contribute to regulating the elasticity of the vascular wall.

Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome

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Hoang, Vanessa; Bi, Jiangjiang; Mohankumar, Sheba M.; Vyas, Arpita K.

2015-01-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of 5–8%. Type 2 diabetes and cardiovascular disease (CVD) are its long-term complications. Targeted therapies addressing both these complications together are lacking. Glucagon like peptide-1 (GLP-1) agonists that are used to treat type 2 diabetes mellitus have beneficial effects on the cardiovascular system. Hence we hypothesized that a GLP-1 agonist would improve both cardiovascular and metabolic outcomes in PCOS. To test this hypothesis, we used an established rat model of PCOS. Prepubertal female Sprague Dawley rats were sham-implanted or implanted s.c. with dihydrotestosterone (DHT) pellets (90 day release; 83μg/day). At 12 wks of age, sham implanted rats received saline injections and the DHT treated animals were administered either saline or liraglutide (0.2mg/kg s.c twice daily) for 4 weeks. Subgroups of rats were implanted with telemeters between 12-13 weeks of age to monitor blood pressure. DHT implanted rats had irregular estrus cycles and were significantly heavier than the control females at 12 weeks (mean± SEM 251.9±3.4 vs 216.8±3.4 respectively; pDHT treated rats significantly decreased body weight (mean± SEM 294.75 ±3.2 in DHT+ saline vs 276.25±2.7 in DHT+ liraglutide group respectively; pDHT implanted rats significantly improved glucose excursion during oral glucose tolerance test (area under the curve: DHT+ saline 28674±310 vs 24990± 420 in DHT +liraglutide p DHT rats were hypertensive and liraglutide treatment significantly improved mean arterial pressure. These results suggest that GLP-1 treatment could improve DHT–induced metabolic and blood pressure deficits associated with PCOS. PMID:26010091

Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat.

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Saito, Motoaki; Shimizu, Shogo; Ohmasa, Fumiya; Oikawa, Ryo; Tsounapi, Panagiota; Dimitriadis, Fotios; Kinoshita, Yukako; Satoh, Keisuke

2013-04-01

As increasing evidence suggest that α(1)-blockers prevent benign prostatic hyperplasia related overactive bladder and nocturia in the human, we investigated the effects of silodosin and naftopidil on hypertension-related bladder dysfunction in the spontaneously hypertensive rat (SHR) model. Twelve-week-old male SHRs received no treatment or treatment with silodosin (100 µg/kg, p.o.) or naftopidil (10 or 30 mg/kg, p.o.) once daily for 6 weeks. Wistar rats were used as normotensive controls. After 6-week treatment, voiding functions were estimated by metabolic cages (dark- and light-cycle separately) and cystometric studies. Furthermore, the bladder blood flow (BBF) was measured employing the hydrogen clearance method. SHRs showed significant increases in micturition frequency, and decreases in BBF and single voided volume in both metabolic cages and cystometrograms compared to the Wistar group. Treatment with silodosin normalized the decreased BBF, and treatment with naftopidil increased the BBF in a dose-dependent manner in the SHR group. Although treatment with silodosin and the high dose of naftopidil significantly inhibited micturition frequency in one day, only treatment with the high dose of naftopidil significantly inhibited micturition frequency and urine production in the light-cycle compared to the non-treated SHRs. Although treatment with silodosin and the high dose of naftopidil significantly increased single voided volume, only treatment with silodosin significantly inhibited non-voiding contractions in the cystometrgrams. Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production. Copyright © 2012 Wiley Periodicals, Inc.

Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

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Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

2004-07-02

Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

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Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

2017-05-01

Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

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

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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.

The Antihypertensive Effects of Hydroalcoholic Extract of Allium Eriophyllum Leaves on Rats with Simultaneous Type 2 Diabetes and Renal Hypertension

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Masoud Mozafari

2015-03-01

Full Text Available Background: Some species of Allium family are known to have antihypertensive, anti-diabetic, and lipid lowering effects. Objectives: This study aimed to examine the possible mechanisms of antihypertensive, anti-diabetic, and anti-lipid activities of Allium eriophyllum which grows in Fars province, Iran in a rat model of simultaneous type 2 diabetes and renal hypertension. Materials and Methods: This study was conducted on six groups of male Spargue-Dawley rats each containing 8 - 10 animals, including a sham-control, a diabetic, a renal hypertensive, and three simultaneously hypertensive–diabetic groups receiving vehicle or 30 or 100 mg/kg/day hydroalcoholic extract of Allium eriophyllum. Four weeks after induction of diabetes, renal hypertension was induced and the animals started receiving the vehicle or extract for the subsequent four weeks. Afterwards, blood pressure, fasting blood sugar, serum cholesterol, triglyceride, and markers of oxidative stress were measured, and isolated studies were performed on aortic rings. Results: Systolic blood pressure, heart rate, fasting blood sugar, maximal response, and effective concentrations 50 (EC50 of phenylephrine and acetylcholine of the hypertensive-diabetic group receiving vehicle were significantly higher compared to those of the sham-control group, and treatment with the extract led to a significant reduction in these variables. Moreover, serum superoxide dismutase and glutathione reductase and maximal response of acetylcholine were significantly lower in the hypertensive-diabetic group receiving vehicle in comparison to the sham-control group, and treatment with the extract significantly reduced these variables. Conclusions: The present study findings indicated that antihypertensive, anti-diabetic, and anti-lipid effects of the extract might be partly due to its antioxidant mechanism. It was also revealed that its antihypertensive effects may be additionally mediated by improving the release

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

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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

Affective disorders among patients with borderline personality disorder.

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Sjåstad, Hege Nordem; Gråwe, Rolf W; Egeland, Jens

2012-01-01

The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect

Affective disorders among patients with borderline personality disorder.

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Hege Nordem Sjåstad

Full Text Available BACKGROUND: The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. METHODS: In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773, we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043 had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636. Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. RESULTS: More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. CONCLUSIONS: The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than

Affective Disorders among Patients with Borderline Personality Disorder

Science.gov (United States)

Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

2012-01-01

Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

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Li, Hong-Bao [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Ma, Le [Department of Public Health, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Miao, Yu-Wang [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Lu, Yan [Department of Clinical Laboratory, Sanaitang Hospital, Lanzhou 730030 (China); Song, Xin-Ai [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (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)

2014-09-01

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91{sup phox}) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension.

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

International Nuclear Information System (INIS)

Li, Hong-Bao; Qin, Da-Nian; Ma, Le; Miao, Yu-Wang; Zhang, Dong-Mei; Lu, Yan; Song, Xin-Ai; Zhu, Guo-Qing; Kang, Yu-Ming

2014-01-01

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91 phox ) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension

Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension.

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Durgan, David J; Ganesh, Bhanu P; Cope, Julia L; Ajami, Nadim J; Phillips, Sharon C; Petrosino, Joseph F; Hollister, Emily B; Bryan, Robert M

2016-02-01

Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (Phypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; Phypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension. © 2015 American Heart Association, Inc.