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  1. CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERSENSITIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE

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    CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERTENSIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE. SS Nadadur UP Kodavanti, Pulmonary Toxicology Branch, ETD, ORD, NHEERL, US Environmental Protection Agency, Research Triangle Park, NC 27711.

  2. 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.

  3. Surgical management of spontaneous hypertensive brainstem hemorrhage

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    Bal Krishna Shrestha

    2015-09-01

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

  4. 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

  5. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

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

    2004-11-01

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

  7. 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...

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

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    Octávio Barbosa Neto

    2013-03-01

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

  9. Pathogenesis of hypercalciuria in spontaneously hypertensive rats.

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

    1986-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  11. 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

  12. Nitric oxide synthase isoforms in spontaneous and salt hypertension

    Czech Academy of Sciences Publication Activity Database

    Hojná, Silvie; Kuneš, Jaroslav; Zicha, Josef

    2007-01-01

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

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

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

    2016-03-01

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

  14. 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...

  15. 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

  16. Acanthopanax divaricatus var. chiisanensis reduces blood pressure via the endothelial nitric oxide synthase pathway in the spontaneously hypertensive rat model.

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    Park, Soo-Yeon; Do, Gyeong-Min; Lee, Sena; Lim, Yeni; Shin, Jae-Ho; Kwon, Oran

    2014-09-01

    In this study, we investigated the antihypertensive effects of Acanthopanax divaricatus var. chiisanensis extract (AE) and its active compound, acanthoside D (AD), on arterial blood pressure (BP) in vivo and endothelial function in vitro. We hypothesized that AE has antihypertensive effects, which is attributed to enhancement of endothelial function via the improvement of nitric oxide synthesis or the angiotensin II (Ang II) response. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly divided into 7 groups and then fed the following diets for 14 weeks: WKY fed a normal diet (WN); SHR fed a normal diet (SN); SHR fed a high-cholesterol (HC) diet (SH); SHR fed a HC diet with AE of 150, 300, 600 mg/kg body weight (SH-L, SH-M, SH-H); and SHR fed an HC diet with AD of 600 μg/kg body weight (SH-D). Blood pressure was significantly reduced in the SH-H compared with the SH from week 10 until week 14; BP was also significantly decreased in the SHR fed a HC diet with AE of 300 at week 14. Aortic wall thickness showed a tendency to decrease by AE and AD treatment. The SH-H showed increased endothelial nitric oxide synthase (eNOS) expression in the intima and media, compared with the SH. Furthermore, a significant increase in intracellular nitric oxide production was induced by AE and AD treatment in human umbilical vein endothelial cells. A significant increase of phospho-eNOS was found with a high dose of AE in human umbilical vein endothelial cells but not with AD. These results suggest that AE can regulate BP and improve endothelial function via eNOS-dependent vasodilation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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

  19. 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.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  1. Recent progress in the genetics of spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

  2. 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

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

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    Nobutomo Ikarashi

    2018-03-01

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

  4. Age-related weakening of baroreflex-mediated sympathetic activity in spontaneously hypertensive rats in response to blood pressure reduction.

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    Prados, P; Santa, T; Fukushima, T; Homma, H; Kasai, C; Martin, M A; del Castillo, B; Imai, K

    1998-09-01

    Nicardipine, a dihydropyridine type calcium channel blocker, was infused into 4-, 6-, and 23-wk-old spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia and ventilation, n = 4) through the left femoral vein, resulting in the reduction of blood pressure. In each rat, mean arterial blood pressure, heart rate, and the concentration of plasma catecholamines (CAs), norepinephrine (NE), and epinephrine (E) were concomitantly determined, and the correlations between these three variables were studied. During the infusion of nicardipine, the plasma concentration of CAs was measured with an automatic detection system in blood samples collected from the right femoral artery of each rat. The reduction in blood pressure induced by nicardipine brought about an increase in plasma CA levels. The blood pressure correlated well with the logarithm of plasma NE or E concentration according to the formula Y= -alpha log (X) + m (Y, blood pressure; X, concentration of plasma NE or E; a, slope; and m, intercept). The slopes (as) of 6-wk-old and 23-wk-old SH rats were significantly greater than those of aged-matched WKY rats, meaning that the increment in plasma CAs in response to a decrease in blood pressure was smaller in SH than in WKY rats of similar ages. However, no significant differences were found between the as of 4-wk-old SH and WKY rats. We conclude that the increment in the baroreflex-mediated sympathetic activity in response to a drop in blood pressure induced by nicardipine is similar or greater in prehypertensive SH than in normotensive WKY 4-wk-old rats, while the increment becomes smaller in SH rats with the onset of hypertension (6-wk-old rats), and is much less in fully hypertensive adult (23-wk-old) SH rats than in age-matched WKY rats. On the basis of these findings and previous data obtained by neurography, we conclude that plasma CAs can be used to evaluate baroreflex-mediated sympathetic

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

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    Foster Martyn

    2009-11-01

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

  6. 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.

  7. 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.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dennis H Lau

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

  10. Abnormalities of glucose metabolism in spontaneously hypertensive rats

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    Gouveia L.M.F.B.

    2000-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    1984-01-01

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

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

    NARCIS (Netherlands)

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

    1994-01-01

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

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

    Science.gov (United States)

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

    2013-01-04

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

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

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    Xinsheng Lai

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

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

    Science.gov (United States)

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

    2009-09-01

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

  17. 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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rachel Melo Ribeiro

    2014-01-01

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

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Virginia Alice Vieira da Costa

    2008-02-01

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

  2. 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

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

    Science.gov (United States)

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

    1985-01-01

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

  4. 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.

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

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    Philip M. Coan

    2017-03-01

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

  6. Characterizing operant hyperactivity in the Spontaneously Hypertensive Rat

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    Hill Jade C

    2012-01-01

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

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

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    Bolanle C. Akinwumi

    2017-02-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

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

  9. 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

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

    Science.gov (United States)

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

    2013-06-01

    Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (peffect of the catalase inhibitor treatment was stronger in the fresh air condition (pcatalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Vitor E. Valenti

    2013-06-01

    Full Text Available OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY rats and spontaneously hypertensive rats (SH (16 weeks old were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V. The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm. The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus and a depressor dose of sodium nitroprusside (50 μg/kg, bolus. Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05 to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05. CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

  13. 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

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  15. 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

  16. 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

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

    Czech Academy of Sciences Publication Activity Database

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

    2006-01-01

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

  18. 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

  19. 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:

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

    Czech Academy of Sciences Publication Activity Database

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

    2006-01-01

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

  1. Mechanism of indapamide-induced prevention of spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2012-12-01

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

  4. Pharmacokinetic-pharmacodynamic modeling of the antihypertensive interaction between azilsartan medoxomil and chlorthalidone in spontaneously hypertensive rats.

    Science.gov (United States)

    Kumar Puttrevu, Santosh; Ramakrishna, Rachumallu; Bhateria, Manisha; Jain, Moon; Hanif, Kashif; Bhatta, Rabi Sankar

    2017-05-01

    A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

  5. Long-Term Regulation of the Local Renin-Angiotensin System in the Myocardium of Spontaneously Hypertensive Rats by Feeding Bioactive Peptides Derived from Spirulina platensis.

    Science.gov (United States)

    Pan, Huanglei; She, Xingxing; Wu, Hongli; Ma, Jun; Ren, Difeng; Lu, Jun

    2015-09-09

    This study investigated the long-term (8 weeks) anti-hypertensive effects of 10 mg/kg tripeptides isolated from Spirulina platensis, Ile-Gln-Pro (IQP) and Val-Glu-Pro (VEP), and S. platensis hydrolysates (SH) on spontaneously hypertensive rats. The treatment period was 6 weeks, and observation continued for another 2 weeks. After treatment, weighted systolic blood pressure, weighted diastolic blood pressure, left ventricular mass index, and right ventricular mass index of groups treated with IQP, VEP, and SH were significantly lower than those of the group treated with distilled water, even when the treatments had been withdrawn for 2 weeks. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting showed the mRNA expression levels and protein/peptide concentrations of the main components of the renin angiotensin system in myocardium were significantly affected by treatment: angiotensin converting enzyme, angiotensin II, and angiotensin type 1 receptor were down-regulated, whereas angiotensin type 2 receptor, angiotensin converting enzyme 2, angiotensin-(1-7), and Mas receptor were up-regulated.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nai-Chia Fan

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    1988-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga

    2007-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    1992-01-01

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

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

    Science.gov (United States)

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

    2017-03-30

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mitsunori Miyazaki

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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Milanović S.

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Abel Felipe Freitag

    2015-01-01

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

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

    Science.gov (United States)

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

    2013-11-25

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  3. 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...

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

    Science.gov (United States)

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

    2017-11-24

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

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

    Directory of Open Access Journals (Sweden)

    Kaustav Majumder

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

  6. 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.

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

    Science.gov (United States)

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

    1988-01-01

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

  8. 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

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

    Czech Academy of Sciences Publication Activity Database

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

    1999-01-01

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

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

    Science.gov (United States)

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

    2009-07-01

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

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

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H

    1989-01-01

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

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

    Science.gov (United States)

    Kimura, M; Okano, S; Inoué, S

    2000-06-01

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

  13. 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

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

    OpenAIRE

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

    2014-01-01

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

  15. 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 ...

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

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

    OpenAIRE

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

    2006-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Giovanni Ramírez-Torres

    2017-11-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

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    Tsuyoshi Chiba

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  7. 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)

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

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    Joseph Iharinjaka Randriamboavonjy

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  10. 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

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

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    Alves Christiano RR

    2012-04-01

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

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

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    L.F. Azevedo

    2003-11-01

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

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

    Science.gov (United States)

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

    2002-03-08

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

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

    Science.gov (United States)

    Akiyama, Kayo; Sutoo, Den'etsu

    2011-01-03

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

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

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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

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

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    Yanru Sun

    2018-02-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

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

    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

  19. 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.

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

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    Noemi López-Carreras

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

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

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    Alfredo de Souza Bomfim

    2003-07-01

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

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

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    Omotayo O. Erejuwa

    2012-01-01

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

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

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    Luana U. Pagan

    2015-04-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-08-01

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

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

    Science.gov (United States)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  10. 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

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

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    Chen Su-Hong

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

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    Sandra Fernández-Vallinas

    2016-05-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  16. 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.

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

    International Nuclear Information System (INIS)

    Von Dreele, M.M.

    1988-01-01

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

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

    Science.gov (United States)

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

    2008-05-01

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

  19. 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.

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

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H

    1989-01-01

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

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

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    Vincent Chin-Hung Chen

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

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

    Science.gov (United States)

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

    2017-01-01

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

  3. 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.

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

    Science.gov (United States)

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

    2004-06-01

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

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

    Science.gov (United States)

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

    2001-05-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Shumei Mao

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Takahashi Reinaldo N

    2007-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Jingfeng Wang

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-11-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-16

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

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

    Directory of Open Access Journals (Sweden)

    M.T. Durand

    2012-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Abraham T. Girgih

    2014-12-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

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

  19. 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

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

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

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

    OpenAIRE

    Kaprinay B.; Bernatova I.; Sotnikova R.

    2016-01-01

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

  3. 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

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

    Czech Academy of Sciences Publication Activity Database

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

    2017-01-01

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

  5. 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

  6. Insights into the clinical management of the syndrome of supine hypertension--orthostatic hypotension (SH-OH): the Irish Longitudinal Study on Ageing (TILDA).

    Science.gov (United States)

    Romero-Ortuno, Roman; O'Connell, Matthew D L; Finucane, Ciaran; Soraghan, Christopher; Fan, Chie Wei; Kenny, Rose Anne

    2013-07-15

    Our previously proposed morphological classification of orthostatic hypotension (MOH) is an approach to the definition of three typical orthostatic hemodynamic patterns using non-invasive beat-to-beat monitoring. In particular, the MOH pattern of large drop/non-recovery (MOH-3) resembles the syndrome of supine hypertension-orthostatic hypotension (SH-OH), which is a treatment challenge for clinicians. The aim of this study was to characterise MOH-3 in the first wave of The Irish Longitudinal Study of Ageing (TILDA), with particular attention to concurrent symptoms of orthostatic intolerance (OI), prescribed medications and association with history of faints and blackouts. The study included all TILDA wave 1 participants who had a Finometer® active stand. Automatic data signal checks were carried out to ensure that active stand data were of sufficient quality. Characterisation variables included demographics, cardiovascular and neurological medications (WHO-ATC), and self-reported information on comorbidities and disability. Multivariable statistics consisted of logistic regression models. Of the 4,467 cases, 1,456 (33%) were assigned to MOH-1 (small drop, overshoot), 2,230 (50%) to MOH-2 (medium drop, slower but full recovery), and 781 (18%) to MOH-3 (large drop, non-recovery). In the logistic regression model to predict MOH-3, statistically significant factors included being on antidepressants (OR = 1.99, 95% CI: 1.50 - 2.64, P hypertensive patients with cardiovascular medications that were not associated with adverse outcomes in our study. Therefore, the evidence of benefit does not necessarily have to conflict with the evidence of potential harm.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Dekanski Dragana

    2014-01-01

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

  9. 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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-12-30

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

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

    Science.gov (United States)

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

    2011-09-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Farman, N.; Bonvalet, J.P.

    1985-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chang-Shin Park

    2012-04-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    1987-12-01

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

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

    Directory of Open Access Journals (Sweden)

    M.V. Borgo

    2011-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Wugang Zhou

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Estato V.

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wei-Min Luo

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

  4. Hypertension

    Science.gov (United States)

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

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

    Science.gov (United States)

    Kato, Kouki; Fushuku, Seigo; Yamamoto, Yoshio

    2017-07-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Womersley Jacqueline S

    2011-12-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2006-04-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2004-08-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    M.V. Borgo

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-17

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

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

    Science.gov (United States)

    Sanae, Matsuda; Yasuo, Aoyagi

    2013-06-12

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

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

    Science.gov (United States)

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

    2015-01-01

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

  2. 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

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

    Science.gov (United States)

    Berg, Torill

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Torill eBerg

    2016-03-01

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

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

    Science.gov (United States)

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

    2017-06-03

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

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

    Directory of Open Access Journals (Sweden)

    Eugênia Abrantes de Figueiredo

    2017-06-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Russell Vivienne A

    2009-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Soto-Rodríguez, Ida

    2011-03-01

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

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

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

    Directory of Open Access Journals (Sweden)

    Xavier eLópez-Gil

    2014-07-01

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

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

    Directory of Open Access Journals (Sweden)

    G. Chandran

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Juan-Juan Xin

    2017-01-01

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

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

    Science.gov (United States)

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

    2016-02-08

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

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

    OpenAIRE

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  17. 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.

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

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-03-02

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ming-Chou Cheng

    2014-06-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

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    A.R. Rodrigues

    2011-06-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

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

    2005-06-01

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

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

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    Hiroshi Yao

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

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

    Science.gov (United States)

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

    2007-06-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2012-05-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

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    Shehu Muhammad Auwal

    2017-12-01

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

  18. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

    Science.gov (United States)

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-10-07

    High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.

  19. 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

  20. Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

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    Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

    1986-03-05

    EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A/sub 4/ hydrolase activity, plasma renin activity (PRA), urinary levels of TxB/sub 2/ and 6-keto-PGF/sub 1..cap alpha../ and aortic conversion of (/sup 14/C)-AA to (/sup 14/C)-6-keto-PGF/sub 1..cap alpha../ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P < 0.001) and retarded the development of hypertension in young SHR rats (178 +/- 6 vs. 218 +/- 4 mmHg in controls, p < 0.001). Platelets showed decreased responsiveness to ADP (3 ..mu..M) and glomerular LTA/sub 4/ hydrolase activity was inhibited. PRA and urinary levels of TxB/sub 2/ and 6-keto-PGF/sub 1..cap alpha../ were not changed. Similarly, there was no change in aortic conversion of (/sup 14/C)-AA to (/sup 14/C)-6-keto-PGF/sub 1..cap alpha../ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function.

  1. Features of the alpha-cell population organization in pancreas of spontaneously hypertensive rats (SHR

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    T. V. Abramova

    2017-08-01

    Full Text Available Alpha cells of pancreatic islets constitute the second largest population of pancreatic endocrinocytes, and the glucagon synthesized in them plays an important role in the regulation of glucose homeostasis. At the same time, glucagon-suppressive therapy is defined as the strategically main source of success of therapy for patients with type 2 diabetes mellitus. In clinical practice, diabetes is often associated with hypertension in the metabolic syndrome, which causes interest in the pathophysiology of α-endocrinocytes. The aim of the study was to investigate the distribution parameters of α-cells in the pancreatic islets of SHR and to characterize the morphological and functional state of glucagon-synthesizing endocrinocytes Materials and methods. In the histological sections of the pancreas, glucagon was detected by the immunofluorescence method; the area of pancreatic islets, as well as the number of α-cells in them, the concentration of immunoreactive glucagon in these cells, the specific indices of the distribution of islets, α-cells and glucagon per unit area of the gland. The results were processed with a package of statistical programs, to assess the reliability of the differences in the groups, the Student’s t-test and the Wilcoxon W-test were used. Results. In normoglycemic SHR, the number of islets containing glucagon-synthesizing α-cells was 10% more (p <0.05 than in normotensive Wistar rats. In the pancreatic tissue, single α-endocrine cells were found in rats of both lines, not forming separate islets. In giant islets of SHR there were 72% more α-endocrine cells than in Wistar rats, and in large islets this difference was twofold. Accordingly, α-cells of these islets contributed significantly to higher glucagon levels in the pancreas of hypertensive rats: in giant islets, the amount of the hormone was 80%, and in large islets – 3.6 times higher than in normotensive rats. In this paper we discuss the mechanisms that lead

  2. Inhibition of NADPH Oxidase-Dependent Oxidative Stress in the Rostral Ventrolateral Medulla Mediates the Antihypertensive Effects of Acupuncture in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Wang, Xue-Rui; Yang, Jing-Wen; Ji, Cai-Shuo; Zeng, Xiang-Hong; Shi, Guang-Xia; Fisher, Marc; Liu, Cun-Zhi

    2018-02-01

    Oxidative stress in the rostral ventrolateral medulla (RVLM), where the sympathetic nervous control center is located, contributes to neural mechanisms of hypertension. Acupuncture was previously reported to favorably affect high blood pressure. However, little is known about the effect of acupuncture on oxidative stress-modulated mechanisms in hypertension. This study was designed to evaluate the hypothesis that acupuncture exerts an antihypertensive effect via ameliorating oxidative stress and the redox-sensitive pathway in the RVLM of spontaneously hypertensive rats. Two weeks of acupuncture reduced blood pressure and sympathetic nervous system activity in spontaneously hypertensive rats. Oxidative stress in the RVLM was alleviated by acupuncture, accompanied by a decrease in nicotinamide adenine dinucleotide phosphate oxidase activity and expression of its subunits. Acupuncture significantly altered the mitogen-activated protein kinases signaling pathway as assessed by pathway enrichment analysis in a gene chip assay. The phosphorylation of p38 mitogen-activated protein kinases and extracellular signal-regulated protein kinase 1/2, but not Jun N-terminal kinase, was downregulated by acupuncture. Microinjection bilaterally of the superoxide dismutase mimetic tempol, nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin, or diphenyleneiodonium chloride into the RVLM mimicked the antihypertensive effect of acupuncture. In contrast, the nicotinamide adenine dinucleotide phosphate oxidase agonist tetrabromocinnamic acid abolished the beneficial effects of acupuncture. Furthermore, injection of capsaicin or surgical sectioning of the sciatic nerve abolished the antihypertensive effect of acupuncture. We conclude that acupuncture decreases high blood pressure and nicotinamide adenine dinucleotide phosphate oxidase in the RVLM of spontaneously hypertensive rats. The mitogen-activated protein kinases and the sciatic nerve are involved in the mechanism

  3. Caffeine improves spatial learning deficits in an animal model of attention deficit hyperactivity disorder (ADHD) -- the spontaneously hypertensive rat (SHR).

    Science.gov (United States)

    Prediger, Rui D S; Pamplona, Fabrício A; Fernandes, Daniel; Takahashi, Reinaldo N

    2005-12-01

    The spontaneously hypertensive rat (SHR) is generally considered to be a suitable genetic model for the study of attention deficit hyperactivity disorder (ADHD), since it displays hyperactivity, impulsivity, poorly sustained attention, and deficits in learning and memory processes. Converging evidence suggests a primary role of disturbance in the dopaminergic neurotransmission in ADHD patients and in SHR, and in addition, some studies have also demonstrated alterations in adenosinergic neurotransmission in SHR. In the present study, adult female Wistar (WIS) and SHR rats received caffeine (1-10 mg/kg i.p.) 30 min before training, immediately after training, or 30 min before a test session in the spatial version of the Morris water maze. The effect of caffeine administration on WIS and SHR blood pressure was also measured. SHR needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of WIS rats in the test session (48 h later), demonstrating a selective deficit in spatial learning. Pre-training administration of caffeine (1-10 mg/kg i.p.) improved this spatial learning deficit in SHR, but did not alter the WIS performance. In contrast, post-training administration of caffeine (3 mg/kg i.p.) did not alter the SHR test performance, but increased memory retention in WIS rats. No dose of caffeine tested altered the mean blood pressure of WIS or SHR. These results demonstrate a selective spatial learning deficit in SHR which can be attenuated by pre-training administration of caffeine. In addition, the present findings indicate that the spatial learning deficit in SHR is not directly related to hypertension.

  4. Renal proximal tubular reabsorption is reduced in adult spontaneously hypertensive rats: roles of superoxide and Na+/H+ exchanger 3.

    Science.gov (United States)

    Panico, Carolina; Luo, Zaiming; Damiano, Sara; Artigiano, Francesca; Gill, Pritmohinder; Welch, William J

    2009-12-01

    Proximal tubule reabsorption is regulated by systemic and intrinsic mechanisms, including locally produced autocoids. Superoxide, produced by NADPH oxidase enhances NaCl transport in the loop of Henle and the collecting duct, but its role in the proximal tubule is unclear. We measured proximal tubule fluid reabsorption (Jv) in WKY rats and compared that with Jv in the spontaneously hypertensive rat (SHR), a model of enhanced renal superoxide generation. Rats were treated with the NADPH oxidase inhibitor apocynin (Apo) or with small interfering RNA for p22(phox), which is the critical subunit of NADPH oxidase. Jv was lower in SHR compared with Wistar-Kyoto rats (WKY; WKY: 2.3+/-0.3 vs SHR: 1.1+/-0.2 nL/min per millimeter; n=9 to 11; P<0.001). Apo and small interfering RNA to p22(phox) normalized Jv in SHRs but had no effect in WKY rats. Jv was reduced in proximal tubules perfused with S-1611, a highly selective inhibitor of the Na(+)/H(+) exchanger 3, the major Na(+) uptake pathway in the proximal tubule, in WKY rats but not in SHRs. Pretreatment with Apo restored an effect of S-1611 to reduce Jv in the SHRs (SHR+Apo: 2.9+/-0.4 vs SHR+Apo+S-1611: 1.0+/-0.3 nL/min per millimeter; P<0.001). However, because expression of the Na(+)/H(+) exchanger 3 was similar between SHR and WKY rats, this suggests that superoxide affects Na(+)/H(+) exchanger 3 activity. Direct microperfusion of Tempol or Apo into the proximal tubule also restored Jv in SHRs. In conclusion, superoxide generated by NADPH oxidase inhibits proximal tubule fluid reabsorption in SHRs. This finding implies that proximal tubule fluid reabsorption is regulated by redox balance, which may have profound effects on ion and fluid homeostasis in the hypertensive kidney.

  5. Effects of kimchi supplementation on blood pressure and cardiac hypertrophy with varying sodium content in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Seung-Min; Cho, Yoonsu; Chung, Hye-Kyung; Shin, Dong-Hyuk; Ha, Woel-Kyu; Lee, Sang-Chul; Shin, Min-Jeong

    2012-08-01

    We tested the effects of dietary intake of freeze-dried Korean traditional fermented cabbage (generally known as kimchi) with varying amounts of sodium on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Wistar-Kyoto rats (WKY), as a control group, received a regular AIN-76 diet, and the SHRs were divided into four groups. The SHR group was fed a regular diet without kimchi supplementation, the SHR-L group was fed the regular diet supplemented with low sodium kimchi containing 1.4% salt by wet weight, which was provided in a freeze-dried form, the SHR-M group was supplemented with medium levels of sodium kimchi containing 2.4% salt, and the SHR-H group was supplemented with high sodium kimchi containing 3.0% salt. Blood pressure was measured over 6 weeks, and cardiac hypertrophy was examined by measuring heart and left ventricle weights and cardiac histology. SHRs showed higher blood pressure compared to that in WKY rats, which was further elevated by consuming high sodium containing kimchi but was not influenced by supplementing with low sodium kimchi. None of the SHR groups showed significant differences in cardiac and left ventricular mass or cardiomyocyte size. Levels of serum biochemical parameters, including blood urea nitrogen, creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sodium, and potassium were not different among the groups. Elevations in serum levels of aldosterone in SHR rats decreased in the low sodium kimchi group. These results suggest that consuming low sodium kimchi may not adversely affect blood pressure and cardiac function even under a hypertensive condition.

  6. Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats.

    Science.gov (United States)

    Ahmad, Fiaz Ud Din; Sattar, Munavvar A; Rathore, Hassaan A; Tan, Yong Chia; Akhtar, Safia; Jin, Oh Hui; Pei, Yen Pei; Abdullah, Nor A; Johns, Edward J

    2014-05-01

    Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n=6) were treated for 4 weeks either as controls or received NaHS (SHR+NaHS), tempol (SHR+Tempol), or NaHS plus tempol (SHR+NaHS +Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all ptempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20-22% vs. ∼11-15% and ∼10-14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all ptempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.

  7. Receptor cleavage and P-selectin-dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat

    Science.gov (United States)

    Chen, Angela Y.; Ha, Jessica N.; DeLano, Frank A.; Schmid-Schönbein, Geert W.

    2012-01-01

    The SHR, a genetic model for hypertension and the metabolic syndrome, has attenuated leukocyte adhesion to the postcapillary endothelium by an unknown mechanism. Based on recent evidence of elevated levels of MMPs in plasma and on microvascular endothelium of the SHR with cleavage of several receptor types, we hypothesize that the reduced leukocyte-endothelial interaction is a result of enhanced proteolytic cleavage of P-selectin on the postcapillary endothelium and PSGL-1 on leukocytes. The attenuated rolling interactions of SHR leukocytes with the endothelium were restored by chronic treatment with a broad-spectrum MMP inhibitor (CGS) for 24 weeks. The SHR MMP levels, in plasma and mesentery, as well as the systolic blood pressure, decreased significantly with treatment. In the SHR mesentery, labeling of P-selectin in the postcapillary venules by immunohistochemistry demonstrated, on average, a 31% lower extracellular P-selectin density compared with the normotensive WKY. A significantly lower extracellular PSGL-1 density on the membranes of SHR neutrophils compared with the WKY also supported our hypothesis. In vivo stimulation of the mesenteric postcapillary venules with histamine demonstrated that the SHR had an attenuated response, as measured by leukocyte rolling velocity on the endothelium. The reduced P-selectin and PSGL-1 density, on SHR postcapillary endothelium and on SHR leukocytes, respectively, was restored significantly by chronic MMP inhibition. The impaired ability of SHR leukocytes to reduce rolling velocity upon inflammatory stimulation led to fewer firmly adhered leukocytes to the endothelium as a contributor to immune suppression. PMID:22566571

  8. Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

    International Nuclear Information System (INIS)

    Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

    1986-01-01

    EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A 4 hydrolase activity, plasma renin activity (PRA), urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ and aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P 4 hydrolase activity was inhibited. PRA and urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ were not changed. Similarly, there was no change in aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function

  9. Effects of PPARγ Agonist Pioglitazone on Redox-Sensitive Cellular Signaling in Young Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Ima Dovinová

    2013-01-01

    Full Text Available PPARγ receptor plays an important role in oxidative stress response. Its agonists can influence vascular contractility in experimental hypertension. Our study was focused on the effects of a PPARγ agonist pioglitazone (PIO on blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling at the central (brainstem, BS and peripheral (left ventricle, LV levels in young prehypertensive rats. 5-week-old SHR were treated either with PIO (10 mg/kg/day, 2 weeks or with saline using gastric gavage. Administration of PIO significantly slowed down blood pressure increase and improved lipid profile and aortic relaxation after insulin stimulation. A significant increase in PPARγ expression was found only in BS, not in LV. PIO treatment did not influence NOS changes, but had tissue-dependent effect on SOD regulation and increased SOD activity, observed in LV. The treatment with PIO differentially affected also the levels of other intracellular signaling components: Akt kinase increased in the the BS, while β-catenin level was down-regulated in the BS and up-regulated in the LV. We found that the lowering of blood pressure in young SHR can be connected with insulin sensitivity of vessels and that β-catenin and SOD levels are important agents mediating PIO effects in the BS and LV.

  10. Hypertension

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for hypertension hyperlipidemia. The data is provided by three managed care organizations in Allegheny County...

  11. Rhodiola-water extract induces β-endorphin secretion to lower blood pressure in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Wei-Jing; Chung, Hsien-Hui; Cheng, Yung-Ze; Lin, Hung Jung; Cheng, Juei-Tang

    2013-10-01

    Rhodiola rosea (Rhodiola) is grown at high altitudes and northern latitudes. It is mainly used clinically as an adaptogen, but antihypertensive effects have been reported for the extract. These have not been well investigated, so in the present study, we evaluated the effect of Rhodiola-water extract on blood pressure in spontaneously hypertensive rats (SHRs) and investigated the potential mechanism(s) for this action. In conscious male SHRs, systolic blood pressure (SBP) and heart rate were recorded using the tail-cuff method. Plasma β-endorphin was measured by enzyme-linked immunosorbent assay. Rhodiola-water extract decreased SBP in SHRs in a dose-dependent manner, and this action was more significant than that in normal group named Wistar-Kyoto (WKY) rats. This reduction of SBP in SHRs was inhibited by pretreatment with the selective opioid μ-receptor antagonist, cyprodime, but not by naloxonazine, an antagonist specific to opioid μ1-receptor. Also, the SBP-lowering action of Rhodiola-water extract was attenuated in adrenalectomized SHRs. Moreover, Rhodiola-water extract dose-dependently increased β-endorphin release in SHRs, and the elevation of β-endorphin in SHRs was higher than that in WKY. Thus, we suggest that Rhodiola-water extract can induce release of β-endorphin to lower SBP in SHRs. Copyright © 2012 John Wiley & Sons, Ltd.

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

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    Yao Hiroshi

    2012-07-01

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

  13. The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Matsuu, Mutsumi; Shichijo; Kazuko; Nakamura, Yasuko; Ikeda, Yuji; Naito, Shinji; Ito, Masahiro; Okaichi, Kumio; Sekine, Ichiro

    2000-01-01

    To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells. (author)

  14. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-01-01

    The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

  16. Effect of arotinolol on hemodynamics and plasma atrial natriuretic peptide at rest and during stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Yamamoto, J; Matsubara, H; Nakai, M

    1989-01-01

    We investigated the effects of chronic treatment with arotinolol, a beta-blocker with weak alpha-blocking potency, on hemodynamics and plasma levels of catecholamines and atrial natriuretic peptide (ANP) at rest and during stress in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. At rest, arotinolol treatment decreased mean arterial pressure (MAP), cardiac index (CI) and heart rate (HR), with no changes in total peripheral resistance index or regional hemodynamics in SHR. Acute stress caused more remarkable hemodynamic changes in SHR. During stress, arotinolol decreased MAP, CI and HR, and reduced myocardial and skeletal muscle flow and splanchnic, renal, cerebral and cutaneous vascular resistance in SHR. Arotinolol's effects were much less in WKY. Stress also increased the plasma catecholamine and ANP levels in SHR. Arotinolol raised these hormones in both strains at rest and in SHR during stress. Thus, arotinolol treatment exerted greater suppressive effects on the resting and stressed hemodynamics in SHR, with associated increases in the plasma catecholamine and ANP levels.

  17. Augmentation of ferulic acid-induced vasorelaxation with aging and its structure importance in thoracic aorta of spontaneously hypertensive rats.

    Science.gov (United States)

    Fukuda, Toshihiko; Kuroda, Takahiro; Kono, Miki; Hyoguchi, Mai; Tanaka, Mitsuru; Matsui, Toshiro

    2015-10-01

    Aging deteriorates vascular functions such as vascular reactivity and stiffness. Thus far, various reports suggest that bioactive compounds can improve vascular functions. However, few age-related studies of natural bioactive compounds are available. The present study attempted to evaluate age-related vasorelaxation of bioactive cinnamic acids, caffeic acid, and ferulic acid using aged rat thoracic aorta. Vasorelaxation was evaluated in thoracic aorta from both 8, 18, and 40 weeks old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) respectively. The result indicated that caffeic acid possessed the vasorelaxation regardless of aging in WKY and SHR. Moreover, the vasorelaxation of ferulic acid enhanced with aging in SHR. The vasorelaxation behavior was acted in an endothelium-independent manner. To access structure importance of enhanced vasorelaxation, analogues of ferulic acid were tested. In 40 weeks old SHR, 3,4-dimethoxycinnamic acid and coniferyl alcohol exhibited equivalent vasorelaxation activity with ferulic acid, providing the structural importance of methoxy-modified 3-position on the phenyl ring and 2-propenoic moiety. These results firstly demonstrated that enhanced vasorelaxation of ferulic acid with aging and 3,4-dimethoxycinnamic acid and coniferyl alcohol, along with ferulic acid, might exhibit the therapeutic potential of vasoactive power with aging.

  18. Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

    Directory of Open Access Journals (Sweden)

    Ryu Jong

    2010-12-01

    Full Text Available Abstract Substrains of the Spontaneously Hypertensive rat (SHR, a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD, have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD. However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA test, and its response on the conditioned place preference (CPP paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj. Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stênio Karlos Alvim Fiorelli

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

  1. Defective fatty acid uptake in the spontaneously hypertensive rat is a primary determinant of altered glucose metabolism, hyperinsulinemia, and myocardial hypertrophy

    Czech Academy of Sciences Publication Activity Database

    Hajri, T.; Ibrahimi, A.; Coburn, C. T.; Knapp jr., F. F.; Kurtz, T.; Pravenec, Michal; Abumrad, N. A.

    2001-01-01

    Roč. 276, č. 26 (2001), s. 23661-23666 ISSN 0021-9258 Grant - others:NIH-OER(US) RO1-DK33301; AHA(US) AHA0020639T; AHA(US) AHA0030345T Institutional research plan: CEZ:AV0Z5011922 Keywords : fatty acid transperter * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.258, year: 2001

  2. Fumaric Acid Esters Can Block Pro-Inflammatory Actions of Human CRP and Ameliorate Metabolic Disturbances in Transgenic Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

    Roč. 9, č. 7 (2014), e101906 E-ISSN 1932-6203 R&D Projects: GA MZd(CZ) NT14325; GA MŠk(CZ) LH12061; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fumaric acid esters * C-reactive protein * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  3. Hypertension.

    Science.gov (United States)

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

    2013-03-01

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

  4. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    Directory of Open Access Journals (Sweden)

    Giuseppina Mattace Raso

    Full Text Available Palmitoylethanolamide (PEA, a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR. Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF, and renin angiotensin system (RAS modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the

  5. β- and α2-Adrenoceptor Control of Vascular Tension and Catecholamine Release in Female Normotensive and Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Berg, Torill

    2017-01-01

    As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower blood pressure than male SHR. In male, normotensive rats (WKY), α 2 - and β 1+2 -adrenoceptors (AR) reciprocally controlled catecholamine release and vascular smooth muscle tension. This interaction was malfunctioning in male SHR. The present study analyzed if a favorable shift in the α 2 /β 1+2 AR interaction may represent an antihypertensive protection in females. Female SHR (early hypertension, 12-14 weeks) and age-matched WKY were infused with tyramine (15 min) to stimulate norepinephrine (NE) release through the reuptake transporter, consequently preventing reuptake. Presynaptic control of vesicular release was therefore reflected as differences in overflow to plasma. The released NE increased total peripheral vascular resistance (TPR). The results showed that β 1>2 AR facilitated tyramine-stimulated NE release in both strains, also in the presence of α 2 AR-antagonist (L-659,066). βAR-antagonist (atenolol-β 1 , ICI-118551-β 2 , nadolol-β 1+2 ) had no effect on the increased secretion of epinephrine after L-659,066 in WKY, but β 1>2 AR-antagonist augmented the L-659,066-induced increase in the secretion of epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater effect in WKY than SHR, whereas β 1or2 -selective antagonists did not. One βAR-subtype may therefore substitute for the other. When both β 1+2 AR were blocked, α 2 AR-antagonist still reduced the TPR response in WKY but not SHR. Thus, α 2 /β 1+2 AR reciprocally controlled catecholamine release, with a particular negative β 1 AR-influence on α 2 AR-auto-inhibition of epinephrine secretion in SHR. Moreover, in these female rats, β 1/2 AR-independent α 2 AR-mediated vasoconstriction was seen in WKY but not SHR, but β 1/2 AR-mediated vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also in SHR.

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

    Science.gov (United States)

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

    2000-04-01

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

  7. Overexpression of AT2R in the solitary-vagal complex improves baroreflex in the spontaneously hypertensive rat.

    Science.gov (United States)

    Ruchaya, Prashant J; Speretta, Guilherme F; Blanch, Graziela Torres; Li, Hongwei; Sumners, Colin; Menani, José V; Colombari, Eduardo; Colombari, Débora S A

    2016-12-01

    The aim of this study was to investigate the physiological effects of increased angiotensin II type 2 receptor (AT2R) expression in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus; NTS/DVM) on baroreflex function in non-anaesthetised normotensive (NT) and spontaneously hypertensive rats (SHR). Ten week old NT Holtzman and SHR were microinjected with either an adeno-associated virus expressing AT2R (AAV2-CBA-AT2R) or enhanced green fluorescent protein (control; AAV2-CBA-eGFP) into the NTS/DVM. Baroreflex and telemetry recordings were performed on four experimental groups: 1) NTeGFP, 2) NTAT2R, 3) SHReGFP and 4) SHRAT2R (n=4-7/group). Following in-vivo experimental procedures, brains were harvested for gene expression analysis. Impaired bradycardia in SHReGFP was restored in SHR rats overexpressing AT2R in the NTS/DMV. mRNA levels of angiotensin converting enzyme decreased and angiotensin converting enzyme 2 increased in the NTS/DMV of SHRAT2R compared to SHReGFP. Increased levels of pro-inflammatory cytokine mRNA levels in the SHReGFP group also decreased in the SHRAT2R group. AT2R overexpression did not elicit any significant change in mean arterial pressure (MAP) in all groups from baseline to 4weeks post viral transfection. Both SHReGFP and SHRAT2R showed a significant elevation in MAP compared to the NTeGFP and NTAT2R groups. Increased AT2R expression within the NTS/DMV of SHR was effective at improving baroreflex function but not MAP. We propose possible mediators involved in improving baroreflex are in the ANG II/ACE2 axis, suggesting a potential beneficial modulatory effect of AT2R overexpression in the NTS/DMV of neurogenic hypertensive rats. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Altered heart rate variability in spontaneously hypertensive rats is associated with specific particulate matter components in Detroit, Michigan.

    Science.gov (United States)

    Rohr, Annette C; Kamal, Ali; Morishita, Masako; Mukherjee, Bhramar; Keeler, Gerald J; Harkema, Jack R; Wagner, James G

    2011-04-01

    Exposure to fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] is linked to adverse cardiopulmonary health effects; however, the responsible constituents are not well defined. We used a rat model to investigate linkages between cardiac effects of concentrated ambient particle (CAP) constituents and source factors using a unique, highly time-resolved data set. Spontaneously hypertensive rats inhaled Detroit Michigan, CAPs during summer or winter (2005-2006) for 13 consecutive days. Electrocardiogram data were recorded continuously, and heart rate (HR) and heart rate variability (HRV) metrics were derived. Extensive CAP characterization, including use of a Semicontinuous Elements in Aerosol Sampler (SEAS), was performed, and positive matrix factorization was applied to investigate source factors. Mean CAP exposure concentrations were 518 μg/m(3) and 357 μg/m(3) in the summer and winter, respectively. Significant reductions in the standard deviation of the normal-to-normal intervals (SDNN) in the summer were strongly associated with cement/lime, iron/steel, and gasoline/diesel factors, whereas associations with the sludge factor and components were less consistent. In winter, increases in HR were associated with a refinery factor and its components. CAP-associated HR decreases in winter were linked to sludge incineration, cement/lime, and coal/secondary sulfate factors and most of their associated components. Specific relationships for increased root mean square of the standard deviation of successive normal-to-normal intervals (RMSSD) in winter were difficult to determine because of lack of consistency between factors and associated constituents. Our results indicate that specific modulation of cardiac function in Detroit was most strongly linked to local industrial sources. Findings also highlight the need to consider both factor analytical results and component-specific results when interpreting findings.

  9. Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

    International Nuclear Information System (INIS)

    Cauvin, C.; Hwang, O.; Yamamoto, M.; van Breemen, C.

    1987-01-01

    Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels

  10. Impulsivity in spontaneously hypertensive rats: Within-subjects comparison of sensitivity to delay and to amount of reinforcement.

    Science.gov (United States)

    Orduña, Vladimir; Mercado, Eduardo

    2017-06-15

    Previous research has shown that spontaneously hypertensive rats (SHR) display higher levels of impulsive choice behavior, which is accompanied by a higher sensitivity to the delay of reinforcement, and by a normal sensitivity to the amount of reinforcement. Because those results were based on three different samples of subjects, in the present report we evaluated these three processes in the same individuals. SHR and WIS rats were exposed to concurrent-chains schedules in which the terminal links were manipulated to assess impulsivity, sensitivity to delay, and sensitivity to amount. For exploring impulsivity, a terminal link was associated with a small reinforcer (1 pellet) delivered after a short delay (2s) while the other terminal link was associated with a larger reinforcer (4 pellets) delivered after a longer delay (28s). For assessing sensitivity to delay, both alternatives delivered the same amount of reinforcement (1 pellet) and the only difference between them was in the delay before reinforcement delivery (2s vs 28s). For assessing sensitivity to amount, both alternatives were associated with the same delay (15s), but the alternatives differed in the amount of reinforcement (1 vs 4 pellets). In addition to replicating previously observed effects within-subjects, we were interested in analyzing different aspects of the regularity of rats' actions in the choice task. The results confirmed that previous findings were not a consequence of between-group differences: SHR were more impulsive and more sensitive to delay, while their sensitivity to amount was normal. Analyses of response regularity indicated that SHR subjects were more periodic in their responses to levers and in their feeder entries, had a higher number of short-duration bouts of responding, and made a substantially higher number of switches between the alternatives. We discuss the potential implications of these findings for the possible behavioral mechanisms driving the increased sensitivity

  11. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Hayato Yanagihara

    2016-07-01

    Full Text Available Although telmisartan, an angiotensin II receptor blocker (ARB, has an agonistic action for proliferator-activated receptor (PPAR-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats. To address the issue, telmisartan (2 mg/kg and olmesartan (2 mg/kg, another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR fed a high fat diet (HFD. HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions.

  12. Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

    Science.gov (United States)

    Katakawa, Mayumi; Fukuda, Noboru; Tsunemi, Akiko; Mori, Mari; Maruyama, Takashi; Matsumoto, Taro; Abe, Masanori; Yamori, Yukio

    2016-12-01

    Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

  13. Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

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    S.L. Amaral

    2008-05-01

    Full Text Available Exercise-induced vessel changes modulate arterial pressure (AP in male spontaneously hypertensive rats (SHR. Vascular endothelial growth factor (VEGF is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY rats, 8-9 weeks (200-250 g. Rats were allocated to daily training or remained sedentary for 3 days (N = 23 or 13 weeks (N = 23. After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis and non-locomotor skeletal muscles (temporalis were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days and (SHR = 141%, WKY = 122%, 13 weeks. SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36% simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%. In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%, without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

  14. Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats.

    Science.gov (United States)

    Lopes, P R; Moreira, M C S; Marques, S M; Pinto, I S J; Macedo, L M; Silva, C C; Freiria-Oliveira, A H; Rebelo, A C S; Reis, A A S; Rosa, D A; Ferreira-Neto, M L; Castro, C H; Pedrino, G R

    2016-08-01

    The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280-350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50-60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

  15. Role of hindbrain melanocortin-4 receptor activity in controlling cardiovascular and metabolic functions in spontaneously hypertensive rats.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Hall, John E

    2015-06-01

    Although we previously demonstrated that activation of central nervous system (CNS) melanocortin3/4 receptors (MC3/4R) play a key role in blood pressure (BP) regulation, especially in spontaneously hypertensive rats (SHRs), the importance of hindbrain MC4R is still unclear. In the present study, we examined the cardiovascular and metabolic effects of chronic inhibition of MC3/4R in the hindbrain of SHRs and normotensive Wistar-Kyoto (WKY) rats. Male WKY rats (n = 6) and SHRs (n = 7) were implanted with telemetry probes to measure BP and heart rate (HR) 24 h/day, and an intracerebroventricular cannula was placed into the fourth ventricle. After 10 days of recovery and 5 days of control measurements, the MC3/4R antagonist (SHU-9119) was infused into the fourth ventricle (1 nmol/h) to antagonize hindbrain MC4R for 10 days, followed by a 5-day recovery period. Chronic hindbrain MC3/4R antagonism significantly increased food intake and body weight in WKY rats (17 ± 1 to 35 ± 2 g/day and 280 ± 8 to 353 ± 8 g) and SHRs (19 ± 2 to 35 ± 2 g/day and 323 ± 7 to 371 ± 11 g), and markedly increased fasting insulin and leptin levels while causing no changes in blood glucose levels (99 ± 4 to 87 ± 4 and 89 ± 5 to 89 ± 4 mg/dl, respectively, for WKY rats and SHRs). Chronic SHU-9119 infusion reduced mean arterial pressure and HR similarly in WKY rats (-8 ± 1 mmHg and -47 ± 3 b.p.m.) and SHRs (-11 ± 3 mmHg and -44 ± 3 b.p.m.). These results suggest that although hindbrain MC4R activity contributes to appetite and HR regulation, it does not play a major role in mediating the elevated BP in SHRs.

  16. Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

    Science.gov (United States)

    Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

    2017-01-01

    Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment

  17. Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Bader Michael

    2008-12-01

    Full Text Available Abstract Background Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs following inhalation of UfCPs (24 h, 172 μg·m-3, to assess whether compromised animals (SHR exhibit a different response pattern compared to the previously studied healthy rats (WKY. Methods Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1, blood coagulation (tissue factor, plasminogen activator inhibitor-1, and endothelial function (endothelin-1, and endothelin receptors A and B were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF. Results Increased BP and heart rate (HR by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary and blood (systemic were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p Conclusion Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction

  18. Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?

    Science.gov (United States)

    Kelsen, Jesper; Kjaer, Katrine; Chen, Gang; Pedersen, Michael; Røhl, Lisbeth; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Rønn, Lars Christian B

    2006-12-06

    Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition with parecoxib in spontaneously hypertensive rats (SHRs) subjected to transient middle cerebral artery occlusion (tMCAo). Sixty-four male SHRs were randomized to 90 min of intraluminal tMCAo or sham surgery. Parecoxib (10 mg/kg) or isotonic saline was administered intraperitoneally (IP) during the procedure, and twice daily thereafter. Nineteen animals were euthanized after 24 hours, and each hemisphere was examined for mRNA expression of pro-inflammatory cytokines and COX enzymes by quantitative RT-PCR. Twenty-three tMCAo animals were studied with diffusion and T2 weighted MRI within the first 24 hours, and ten of the SHRs underwent follow-up MRI six days later. Thirty-three SHRs were given 5-bromo-2'-deoxy-uridine (BrdU) twice daily on Day 4 to 7 after tMCAo. Animals were euthanized on Day 8 and the brains were studied with free-floating immunohistochemistry for activated microglia (ED-1), hippocampal granule cell BrdU incorporation, and neuronal nuclei (NeuN). Infarct volume estimation was done using the 2D nucleator and Cavalieri principle on NeuN-stained coronal brain sections. The total number of BrdU+ cells in the dentate gyrus (DG) of the hippocampus was estimated using the optical fractionator. We found a significant reduction in infarct volume in parecoxib treated animals one week after tMCAo (p < 0.03). Cortical ADC values in the parecoxib group were markedly less increased on Day 8 (p < 0.01). Interestingly, the parecoxib treated rats were segregated into two subgroups, suggesting a responder vs. non-responder phenomenon. We found indications of mRNA up-regulation of IL-1beta, IL-6, TNF-alpha and COX-2, whereas COX-1 remained unaffected. Hippocampal granule cell BrdU incorporation was not affected by parecoxib treatment. Presence of ED-1+ activated microglia in the hippocampus was related

  19. Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs

    Directory of Open Access Journals (Sweden)

    Peters Annette

    2010-09-01

    Full Text Available Abstract Rationale Several epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR, a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg. Methods 250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter 2.5-AB collected from an urban background site in Augsburg during September and October 2006 (PM2.5 18.2 μg/m3, 10,802 particles/cm3 were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF, blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed. Results Exposure to 1000 μg of PM2.5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP during 2nd-4th day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg and reduced heart rate (HR on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm. BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2 from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2.5-AB instillation results in an activation of endothelin system (endothelin1, renin-angiotensin system (angiotensin converting enzyme and also coagulation system (tissue factor, plasminogen activator inhibitor-1 in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected. Conclusions Our data suggests that high concentrations of PM2.5-AB

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

    Science.gov (United States)

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

    2008-04-23

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

  1. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

    DEFF Research Database (Denmark)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

    2017-01-01

    in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...... to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect...... of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague...

  2. 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.

  3. Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Julie Carillon

    2016-04-01

    Full Text Available Background: In spontaneously hypertensive rats (SHR, a model of human essential hypertension, oxidative stress is involved in the development of cardiac hypertrophy and fibrosis associated with hypertension. Dietary supplementation with agents exhibiting antioxidant properties could have a beneficial effect in remodeling of the heart. We previously demonstrated a potent anti-hypertrophic effect of a specific melon (Cucumis melo L. concentrate with antioxidant properties in spontaneously hypertensive rats. Relaxin and atrial natriuretic peptide (ANP were reported to reduce collagen deposition and fibrosis progression in various experimental models. Objective: The aim of the present investigation was to test the hypothesis that, beside reduction in oxidative stress, the melon concentrate may act through relaxin, its receptor (relaxin/insulin-like family peptide receptor 1, RXFP1, and ANP in SHR. Design and results: The melon concentrate, given orally during 4 days, reduced cardiomyocyte size (by 25% and totally reversed cardiac collagen content (Sirius red staining in SHR but not in their normotensive controls. Treatment with the melon concentrate lowered cardiac nitrotyrosine-stained area (by 45% and increased by 17–19% the cardiac expression (Western blot of superoxide dismutase (SOD and glutathione peroxidase. In addition, plasma relaxin concentration was normalized while cardiac relaxin (Western blot was lowered in treated SHR. Cardiac relaxin receptor level determined by immunohistochemical analysis increased only in treated SHR. Similarly, the melon concentrate reversed the reduction of plasma ANP concentration and lowered its cardiac expression. Conclusions: The present results demonstrate that reversal of cardiac fibrosis by the melon concentrate involves antioxidant defenses, as well as relaxin and ANP pathways restoration. It is suggested that dietary SOD supplementation could be a useful additional strategy against cardiac hypertrophy

  4. The role of residual blood pressure in antihypertensive effects of captopril treatment in young and adult spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2006-01-01

    Roč. 24, č. S4 (2006), S343-S344 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] R&D Projects: GA MZd(CZ) NR7786 Keywords : blood pressure * captopril * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  5. The pharmacokinetic-pharmacodynamic model of telmisartan and hydrochlorothiazide on blood pressure and plasma potassium after long-term administration in spontaneously hypertensive rats.

    Science.gov (United States)

    Yu, Dan; Chen, Yuancheng; Hao, Kun

    2015-12-01

    A pharmacokinetic-pharmacodynamic model was developed to describe the time course of blood pressure and plasma potassium after long-term telmisartan and/or hydrochlorothiazide administration in spontaneously hypertensive rats. The spontaneously hypertensive rats were administered once daily for 6 weeks. The drug concentration, blood pressure and plasma potassium were monitored for several points. The time courses of blood pressure and plasma potassium were described by indirect response pharmacokinetic-pharmacodynamic model. The synergistic antihypertensive pharmacodynamic interaction between telmisartan and hydrochlorothiazide was observed, which was simulated by the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after co-administration of the two drugs. For plasma potassium, when hydrochlorothiazide administrated alone, the plasma potassium reached to a low steady-state level at 4.64 mmol/L for 6 weeks. The plasma potassium increased to a steady-state level at 4.84 mmol/L after co-administration of telmisartan. The time courses of plasma potassium were successfully characterized by indirect response pharmacokinetic-pharmacodynamic model after long-term administration of telmisartan and/or hydrochlorothiazide. The model captured turnovers of blood pressure and plasma potassium in the different time phases and dose conditions. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  6. Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: possible implications in hypertension.

    Science.gov (United States)

    Congo Carbajosa, Nadia A; Carbajosa, Nadia A Longo; Corradi, Gerardo; Verrilli, María A Lopez; Guil, María J; Vatta, Marcelo S; Gironacci, Mariela M

    2015-01-01

    Aberrations in the ubiquitin-proteasome system (UPS) are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR) and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86 ± 15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2 ± 8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92 ± 22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7 ± 0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasome activity. Proteasome activity was significantly reduced by 67 ± 4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.

  7. Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: possible implications in hypertension.

    Directory of Open Access Journals (Sweden)

    Nadia A Congo Carbajosa

    Full Text Available Aberrations in the ubiquitin-proteasome system (UPS are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86 ± 15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2 ± 8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92 ± 22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7 ± 0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasome activity. Proteasome activity was significantly reduced by 67 ± 4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.

  8. Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias.

    Science.gov (United States)

    Scridon, Alina; Fouilloux-Meugnier, Emmanuelle; Loizon, Emmanuelle; Rome, Sophie; Julien, Claude; Barrès, Christian; Chevalier, Philippe

    2015-01-01

    The timecourse of left atrial Pitx2 down-regulation in the setting of atrial tachyarrhythmias remains unknown. Accordingly, we aimed to assess the age dependency of left atrial Pitx2 expression in an experimental model of spontaneous atrial tachyarrhythmias in rats. Atrial sampling was performed in three groups (n = 4 each) of young (14-week-old), adult (24-week-old), and ageing (48-week-old) spontaneously hypertensive rats (SHRs), in which we previously demonstrated the age dependency of spontaneous atrial tachyarrhythmias, and three groups (n = 4 each) of age-matched normotensive Wistar-Kyoto (WKY) rats. mRNA expression of Pitx2 was studied using real-time polymerase chain reaction. Ageing SHRs presented significantly lower left atrial Pitx2 expressions compared with age-matched WKY rats (P = 0.02), while no significant difference was observed between young or adult SHRs and age-matched WKY rats (both P > 0.05). Among SHRs, Pitx2 expressions showed a progressive, age-dependent decrease (34.9 ± 6.7 in young SHRs, 17.1 ± 3.6 in adult SHRs, and 10.7 ± 1.7 in ageing SHRs, P = 0.04) and were significantly negatively correlated with both age (Spearman r = -0.86, P Pitx2 down-regulation in SHRs. The strong negative correlation between left atrial Pitx2 expression and heart weight among SHRs may indicate a link between long-standing arterial hypertension and Pitx2-related atrial arrhythmogenicity. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  9. [Serial assessment of myocardial thallium perfusion and fatty acid utilization in spontaneously hypertensive rats: assessment by autoradiography and pin-hole imaging].

    Science.gov (United States)

    Sago, M; Nishimura, T

    1989-07-01

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

  10. Comparative effects of captopril and l-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats.

    Science.gov (United States)

    Miguel-Carrasco, José L; Monserrat, María T; Mate, Alfonso; Vázquez, Carmen M

    2010-04-25

    It has been shown that oxidative stress is involved in the pathogenesis of arterial hypertension. The aim of this work was to study and compare the molecular mechanisms of the antioxidant properties of l-carnitine and captopril in spontaneously hypertensive rats (SHR). Antioxidant enzyme activity/regulation (glutathione peroxidase, glutathione reductase and superoxide dismutase) was measured in the erythrocytes and hearts of SHR. The molecular expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase, angiotensin converting enzyme (ACE), angiotensin II type I receptor (AT(1) receptor) and NF-kappaB/IkappaB system was also measured in the hearts of these animals. Both l-carnitine and captopril augmented the antioxidant defense capacity in SHRs. This effect was mediated by an upregulation of antioxidant enzymes, an increase in the plasma total antioxidant capacity and a reduction of lipid peroxidation and superoxide anion production in the heart. The administration of both compounds to hypertensive animals also produced an upregulation of eNOS and a normalization of ACE, angiotensin AT(1) receptor, and the NF-kappaB/IkappaB system expression. In addition, captopril reduced the arterial blood pressure and the relative heart weights back to control values, whereas l-carnitine caused only a partial reduction of blood pressure values and did not alter the cardiac hypertrophy found in SHRs. In conclusion, we have found that l-carnitine and captopril have a similar antioxidant effect in the hearts of hypertensive rats. The molecular regulation of antioxidant enzymes through an inhibition of the renin-angiotensin system and a modulation of the NF-kappaB/IkappaB system seems to be responsible for this antioxidant effect. 2010 Elsevier B.V. All rights reserved.

  11. Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related

    Czech Academy of Sciences Publication Activity Database

    Janega, P.; Kojšová, S.; Jendeková, L.; Babál, P.; Pecháňová, Olga

    2007-01-01

    Roč. 56, č. 6 (2007), s. 825-828 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : indapamide * myocardial fibrosis * genetic hypertension Subject RIV: ED - Physiology Impact factor: 1.505, year: 2007

  12. Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged Wistar-Kyoto and spontaneously hypertensive rats

    Science.gov (United States)

    This study shows that a single exposure to diesel exhaust causes conduction instability in rats that is worse in the presence of hypertension. The RoR assessment is shown to be a valuable tool that can be used to reveal the deleterious effects of air pollution, particularly in th...

  13. Structural remodeling of resistance vessels and age-dependent antihypertensive effects of captopril treatment in spontaneously hypertensive rats (SHR)

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2006-01-01

    Roč. 22, č. 13 (2006), s. 61-61 ISSN 1000-4718. [International Congress of Pathophysiology /5./. 28.06.2006-01.07.2006, Beijing] R&D Projects: GA MZd(CZ) NR7786 Keywords : hypertensive rat * captopril * vessels Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

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

    Science.gov (United States)

    2010-01-01

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

  15. Function of the isolated perfused kidney in young and adult spontaneously hypertensive and Dahl salt-sensitive rats

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana

    2002-01-01

    Roč. 25, č. 5 (2002), s. 315-321 ISSN 1420-4096 R&D Projects: GA ČR GA306/96/1289; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : rat * hypertension Subject RIV: ED - Physiology Impact factor: 0.968, year: 2002

  16. Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Rebeca Caldeira Machado Berger

    Full Text Available Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%, low salt (LS: 0.03%, and high salt diet (HS: 3% until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.

  17. Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sankar, R.; Domer, F.R.; Taylor, B.

    1982-01-01

    Researchers have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure

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

    Science.gov (United States)

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

    2006-12-01

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

  19. Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats.

    Science.gov (United States)

    Negoro, N; Kanayama, Y; Iwai, J; Umetani, N; Nishimura, M; Konishi, Y; Okamura, M; Inoue, T; Takeda, T

    1994-04-12

    To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

  20. Parameter estimation of feedback gain in a stochastic model of renal hemodynamics: differences between spontaneously hypertensive and Sprague-Dawley rats

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Yip, Kay-Pong; Marsh, Donald J

    2006-01-01

    Proximal tubular pressure shows periodic self-sustained oscillations in normotensive rats but highly irregular fluctuations in spontaneously hypertensive rats (SHR). Although we have suggested that the irregular fluctuations in SHR represent low-dimensional deterministic chaos in tubuloglomerular...... mechanisms not included explicitly in the model. In its deterministic version, the model can have chaotic dynamics arising from TGF. The model introduces random fluctuations into a parameter that determines the gain of TGF. The model shows a rich variety of dynamics ranging from low-dimensional deterministic...... oscillations and chaos to high-dimensional random fluctuations. To fit the data from normotensive rats, the model must introduce only a small variation in the feedback gain, and its estimates of that gain agree well with experimental values. These results support the use of the deterministic model of nephron...

  1. Comparison of the sagittal sinus cross-sectional area between patients with multiple sclerosis, hydrocephalus, intracranial hypertension and spontaneous intracranial hypotension: a surrogate marker of venous transmural pressure?

    Science.gov (United States)

    Bateman, Grant A; Lechner-Scott, Jeannette; Copping, Ross; Moeskops, Christopher; Yap, Swee Leong

    2017-07-06

    There is evidence that patients with multiple sclerosis (MS) and hydrocephalus share some common pathophysiological mechanisms. Alterations in CSF pressure are known to affect cerebral venous sinus geometry. To further explore these mechanisms, we measured the superior sagittal sinus (SSS) cross-sectional area 3 cm above the torcular using T2 images in 20 MS, 10 spontaneous intracranial hypotension (SIH), 21 hydrocephalus and 20 idiopathic intracranial hypertension (IIH) patients and compared with 20 matched controls. The SSS area was reduced by 25% in hydrocephalus (p = 0.0008), increased by 22% (p = 0.037) in SIH and unchanged in IIH compared to matched controls. In MS there was a 16% increase in SSS area (p = 0.01).The findings suggest that changes in SSS cross-sectional are common between MS and SIH patients, while in hydrocephalus and IIH these are different.

  2. Mn++-stimulated 3H-inositol incorporation in cultured vascular smooth muscle cells: deficiency in cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Buck, S.H.; Nabika, T.; Lovenberg, W.

    1985-01-01

    Incubation of cultured dissociated aortic smooth muscle cells from Wistar-Kyoto rats (WKY) with Mn++ resulted in a 10-fold stimulation of 3 H-myo-inositol incorporation into membrane phospholipids. The stimulation was temperature and energy dependent. The Mn++ EC50 was 1 mM and maximum stimulation occurred at 10 mM Mn++. Other cations were ineffective. In cells from spontaneously hypertensive rats (SHR), the Mn++ EC50 was unchanged whereas the maximum stimulation of 3 H-inositol incorporation was reduced by 50% compared to cells from parallel WKY cultures. These results suggest that in SHR cultured vascular smooth muscle cells there is a deficiency in an enzymatic process mediating exchange of free inositol with the headgroup inositol of membrane phosphatidylinositol

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

    Science.gov (United States)

    Nováková, Marta; Parkanová, Daniela; Sumová, Alena

    2013-01-01

    The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF) leads to the development of food anticipatory activity (FAA) and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR). The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase), in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock. PMID:24086613

  4. Increased sensitivity of the circadian system to temporal changes in the feeding regime of spontaneously hypertensive rats - a potential role for Bmal2 in the liver.

    Directory of Open Access Journals (Sweden)

    Lenka Polidarová

    Full Text Available The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF leads to the development of food anticipatory activity (FAA and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR. The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase, in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock.

  5. Inactivation of Gi proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Zemančíková, A.; Török, J.; Zicha, Josef; Kuneš, Jaroslav

    2008-01-01

    Roč. 57, č. 2 (2008), s. 299-302 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:VEGA(SK) 2/6150/27 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * adrenergic vasoconstriction * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

  6. 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

  7. Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

    Science.gov (United States)

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-01-01

    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

  8. Angiotensin-(1-7) Blockade Attenuates Captopril- or Hydralazine-Induced Cardiovascular Protection in Spontaneously Hypertensive Rats-Treated with L-NAME

    Science.gov (United States)

    Benter, Ibrahim F.; Yousif, Mariam H. M.; Al-Saleh, Fatemah M.; Chappell, Raj Raghupathy Mark C.; Diz, Debra I.

    2011-01-01

    We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHR) chronically treated with the nitric oxide synthesis inhibitor L-NAME (SHR-L). L-NAME (80 mg/L) administration for three weeks increased mean arterial pressure (MAP) from 196 ± 6 mmHg to 229 ± 3 mmHg (pcaptopril (300 mg/L in drinking water) or hydralazine (1.5 mg/kg/day ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment, and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-L hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery following ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role to effectively buffer the increase in blood pressure and renal injury, as well as the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage. PMID:21326110

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Izabella Silva De Jesus Pinto

    2016-06-01

    Full Text Available IIntrathecal injection of bombesin (BBS promoted hypertensive and sympathoexcitatory effects in normotensive (NT rats. However, the involvement of rostral ventrolateral medulla (RVLM in these responses is still unclear. In the present study, we investigated: (1 the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR; (2 the contribution of RVLM bombesin type 1 receptors (BB1 to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v. were instrumented to record mean arterial pressure (MAP, diaphragm (DIA motor and renal sympathetic nerve activity (RSNA. In NT rats and SHR, BBS (0.3 mM nanoinjected into RVLM increased MAP (33.9 ± 6.6 mmHg and 37.1 ± 4.5 mmHg, respectively; p < 0.05 and RSNA (97.8 ± 12.9 % and 84.5 ± 18.1 %, respectively; p < 0.05. In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7 %; p < 0.05. BB1 receptors antagonist (BIM-23127; 3 mM reduced MAP (-19.9 ± 4.4 mmHg; p < 0.05 and RSNA (-17.7 ± 3.8 %; p < 0.05 in SHR, but not in NT rats (-2.5 ± 2.8 mmHg; -2.7 ± 5.6 %, respectively. These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

  11. Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats.

    Science.gov (United States)

    Girgih, Abraham T; Alashi, Adeola; He, Rong; Malomo, Sunday; Aluko, Rotimi E

    2014-08-01

    This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined. Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0% levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase). Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly (p < 0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054 μg/mL) when compared to control rats that were fed only with casein (0.151 μg/mL). The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.

  12. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

    Science.gov (United States)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

    2017-12-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

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    Dervola Kine S

    2012-12-01

    Full Text Available Abstract Background Previous reports suggest that omega-3 (n-3 polyunsaturated fatty acids (PUFA supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR. SHR dams were given n-3 PUFA (EPA and DHA-enriched feed (n-6/n-3 of 1:2.7 during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY control rats were given control-feed (n-6/n-3 of 7:1. During postnatal days (PND 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms

  14. Selective replacement of mitochondrial DNA increases the cardioprotective effect of chronic continuous hypoxia in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Neckář, Jan; Svatoňová, Anna; Weissová, Romana; Drahota, Zdeněk; Zajíčková, Pavlína; Brabcová, I.; Kolář, D.; Alánová, Petra; Vašinová, Jana; Šilhavý, Jan; Hlaváčková, Markéta; Tauchmannová, Kateřina; Milerová, Marie; Ošťádal, Bohuslav; Červenka, L.; Žurmanová, J.; Kalous, M.; Nováková, Olga; Novotný, J.; Pravenec, Michal; Kolář, František

    2017-01-01

    Roč. 131, č. 9 (2017), s. 865-881 ISSN 0143-5221 R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : chronic hypoxia * heart * hypertension * ischaemia–reperfusion injury * mitochondrial genome * mitochondrial permeability transition pore Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Physiology (including cytology) Impact factor: 4.936, year: 2016

  15. 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.

  16. 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.

  17. Effect of Olea europea L. leaf extract on haemodynamic status and lipid peroxidation in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Miloradović Zoran

    2013-01-01

    Full Text Available Hypertension is one of the main causes of cardiovascular disorders and since ancient times olive tree leaves have been used in its therapy. However the mechanisms of their atihypertensive effect have not been sufficiently explained yet. The main objective of our study was to investigate acute effect of olive tree leaves extract on haemodynamics and lipid peroxidation in rats with congenital hypertension under normal and blocked synthesis of nitric oxide. For the purpose of our research, there were used olive tree leaf extract EFLA® 943 as well as inhibitor of nitric oxide synthase enzyme L-NAME. Nitric oxide synthesis inhibition led to statistically significant increase of mean arterial pressure, reducing heart rate and cardiac output, increase of total vascular resistance and lipid peroxidation in plasma. Treatment by olive leaf extract led to decrease of mean arterial pressure, reducing the frequency and cardiac output, without change in lipid peroxidation. Olive leaf extract under blockade of nitric oxide led to decrease of mean arterial pressure, total peripheral resistance remained high, cardiac output low, and lipid peroxidation significantly increased. General conclusion is that olive leaf extract has a strong antihypertensive effect, decreases cardiac pre and after load and does not influence lipid peroxidation. Under blockade of nitric oxide synthesis, this extract keeps antihypertensive properties, but due to strong endothelial dysfunction, it is unable to regulate increased total peripheral resistance and marked lipid peroxidation. [Projekat Ministarstva nauke Republike Srbije, br. 175096: Ispitivanje antihipertenzivnog potencijala supstanci prirodnog i sintetskog porekla u eksperimentalnim modelima kardiovaskularnih i bubrežnih oboljenja

  18. Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats.

    Science.gov (United States)

    Varagic, Jasmina; Ahmad, Sarfaraz; Voncannon, Jessica L; Moniwa, Norihito; Simington, Stephen W; Brosnihan, Bridget K; Gallagher, Patricia E; Habibi, Javad; Sowers, James R; Ferrario, Carlos M

    2012-09-01

    Increased sympathetic outflow, renin-angiotensin system (RAS) activity, and oxidative stress are critical mechanisms underlying the adverse cardiovascular effects of dietary salt excess. Nebivolol is a third-generation, highly selective β1-receptor blocker with RAS-reducing effects and additional antioxidant properties. This study evaluated the hypothesis that nebivolol reduces salt-induced cardiac remodeling and dysfunction in spontaneous hypertensive rats (SHRs) by suppressing cardiac RAS and oxidative stress. Male SHRs (8 weeks of age) were given an 8% high salt diet (HSD; n = 22), whereas their age-matched controls (n = 10) received standard chow. In a subgroup of HSD rats (n = 11), nebivolol was given at a dose of 10 mg/kg per day by gastric gavage. After 5 weeks, HSD exacerbated hypertension as well as increased left-ventricular weight and collagen deposition while impairing left-ventricular relaxation. Salt-induced cardiac remodeling and dysfunction were associated with increased plasma renin concentration (PRC), cardiac angiotensin II immunostaining, and angiotensin-converting enzyme (ACE)/ACE2 mRNA and activity ratio. HSD also increased cardiac 3-nitrotyrosine staining indicating enhanced oxidative stress. Nebivolol treatment did not alter the salt-induced increase in arterial pressure, left-ventricular weight, and cardiac dysfunction but reduced PRC, cardiac angiotensin II immunostaining, ACE/ACE2 ratio, oxidative stress, and fibrosis. Our data suggest that nebivolol, in a blood pressure-independent manner, ameliorated cardiac oxidative stress and associated fibrosis in salt-loaded SHRs. The beneficial effects of nebivolol may be attributed, at least in part, to the decreased ACE/ACE2 ratio and consequent reduction of cardiac angiotensin II levels.

  19. Super, red palm and palm oleins improve the blood pressure, heart size, aortic media thickness and lipid profile in spontaneously hypertensive rats.

    Science.gov (United States)

    Boon, Chee-Meng; Ng, Mei-Han; Choo, Yuen-May; Mok, Shiueh-Lian

    2013-01-01

    Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension. Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (prats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR. The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR.

  20. The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Dalpiaz, P.L.M.; Lamas, A.Z.; Caliman, I.F. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Medeiros, A.R.S. [Ciências Biológicas e da Saúde, Instituto Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Andrade, T.U. [Departamento de Farmácia, Centro Universitário de Vila Velha, Vila Velha, ES (Brazil); Alves, M.F.; Carmona, A.K. [Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Bissoli, N.S. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2013-02-01

    Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

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

    Science.gov (United States)

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

    2003-02-01

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

  2. Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

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    Kanintra Suwanmanon

    2014-12-01

    Full Text Available In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY rats were randomized into seven groups. Until the 8th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD; Group 2, medium dose of GABA and nattokinase in the SHR (SMD; Group 3, low dose of GABA and nattokinase in the SHR (SLD; Group 4, negative control in the SHR (SD; Group 5, positive control in the SHR (SM; Group 6, high dose of GABA and nattokinase in the WKY (WHD; and Group 7, negative control in the WKY (WD. Distilled water served as the negative control, and captopril (50 mg/kg, a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8th week to the 16th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.

  3. Effects of Acidic Polysaccharides from Gastrodia Rhizome on Systolic Blood Pressure and Serum Lipid Concentrations in Spontaneously Hypertensive Rats Fed a High-Fat Diet

    Science.gov (United States)

    Lee, Ok-Hwan; Kim, Kyung-Im; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

    2012-01-01

    The effects of acidic polysaccharides purified from Gastrodia rhizome on blood pressure and serum lipid levels in spontaneously hypertensive rats (SHR) fed a high-fat diet were investigated. Acidic polysaccharides were purified from crude polysaccharides by DEAE-Sepharose CL-6B. Thirty-six male SHR were randomly divided into three groups: Gastrodia rhizome crude polysaccharide (A), acidic polysaccharide (B) groups, and a control group (C). A 5-week oral administration of all treatment groups was performed daily in 3- to 8-week-old SHRs with a dose of 6 mg/kg of body weight/day. After 5 weeks of treatment, total cholesterol in the acidic polysaccharide group, at 69.7 ± 10.6 mg/dL, was lower than in the crude polysaccharide group (75.0 ± 6.0 mg/dL) and the control group (89.2 ± 7.4 mg/dL). In addition, triglyceride and low-density lipoprotein cholesterol levels in the acidic polysaccharide group were lower than in the crude polysaccharide and control groups. The atherogenic index of the acidic polysaccharide group was 46.3% lower than in the control group. Initial blood pressure after the initial three weeks on the high-fat diet averaged 195.9 ± 3.3 mmHg among all rats. Compared with the initial blood pressure, the final blood pressure in the control group was increased by 22.8 mmHg, whereas it decreased in the acidic polysaccharide group by 14.9 mmHg. These results indicate that acidic polysaccharides from Gastrodia rhizome reduce hypertension and improve serum lipid levels. PMID:22312280

  4. Long-term effect of prazosin administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats.

    Science.gov (United States)

    Kristek, F; Koprdova, R

    2011-06-01

    The sympathetic nervous system belongs to the essential systems participating in blood pressure (BP) regulation. Inhibitory intervention into the key point of its operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously hypertensive rats (SHR) might affect the development of the hypertension in later ontogenic periods. We studied the long-term effect of prazosin administration on the cardiovascular system of young Wistar rats and SHR. Four-week-old animals were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10 mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the plethysmographic method. After six weeks under anaesthesia, the carotid artery was cannulated for BP registration, and the jugular vein was cannulated for administration of drugs. Afterwards, the animals were perfused with a glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left descending coronary artery was processed using electron microscopy. The prazosin administration evoked the following results in both groups: a decrease of BP and heart/body weight ratio, enhancement of hypotensive responses to acetylcholine (0.1 μg, 1 μg, and 10 μg), and an increase in the inner diameter of the coronary artery without changes in wall thickness, cross sectional area (CSA) (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In the SHR group, a reduction was observed in BP increase after noradrenaline (1 μg) application. CSA of endothelial cells which was decreased in the SHR (compared to the control Wistar rats) was increased after prazosin treatment (up to control value). Long-term prazosin administration from early ontogeny partially prevented some pathological alterations in the cardiovascular system of SHR.

  5. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

    Directory of Open Access Journals (Sweden)

    Danijela Karanovic

    Full Text Available Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD. Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger or losartan (angiotensin II type 1 receptor blocker treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS, erythrocyte antioxidant enzymes activities and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities, kidney function and structure in spontaneously hypertensive rats (SHR with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v. twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day, tempol (T,100 mg/kg/day or combined T+L treatment (by gavage during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1 protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4 protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2 protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria, pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  6. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

    Science.gov (United States)

    Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  7. Effect of Clonidine (an antihypertensive drug) treatment on oxidative stress markers in the heart of spontaneously hypertensive rats.

    Science.gov (United States)

    Nik Yusoff, Nik Syamimi; Mustapha, Zulkarnain; Govindasamy, Chandran; Sirajudeen, K N S

    2013-01-01

    Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO) in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C), SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME)]. Rats (SHRC) were administered with Clonidine (0.5 mg kg(-1) day(-1)) from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg(-1) day(-1)) from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP) was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS) (P heart of SHR and SHR+L-NAME.

  8. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

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    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

    2015-03-27

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  9. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

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    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

    2015-01-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

  10. Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in spontaneously hypertensive rats on high-salt diet in a blood-pressure-independent manner.

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    Trenkner, Jörg; Priem, Friedrich; Bauer, Christian; Neumayer, Hans-Hellmut; Raschak, Manfred; Hocher, Berthold

    2002-08-01

    The renal endothelin (ET) system is involved in the pathogenesis of kidney fibrosis as well as blood pressure control by regulating tubular sodium excretion. Long-term effects of ETA receptor blockade on blood pressure and kidney function in spontaneously hypertensive rats (SHRs) on a high-salt diet are unknown. We treated SHRs on a 6% (w/v) NaCl sodium diet (SHR-S) for 48 weeks with the ETA antagonist LU 135252 (whose selectivity for ETA is 150 times greater than for ETB) with 10, 30 and 100 mg x kg(-1) x day(-1) or placebo. The ETA antagonist had at no time-point any effect on blood pressure. Glomerular filtration rate was normal in SHR-S and not altered by LU 135252. However, urinary albumin excretion was markedly reduced by the ETA antagonist (SHR-S, 145+/-50 mg/day; SHR-S+10 mg x kg(-1) x day(-1) LU 135252, 33+/-11 mg/day, Pproteinuria-induced chronic renal failure.

  11. Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats.

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    Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

    2017-01-01

    Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway.

  12. Long-Term Stimulation with Electroacupuncture at DU20 and ST36 Rescues Hippocampal Neuron through Attenuating Cerebral Blood Flow in Spontaneously Hypertensive Rats

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    Gui-Hua Tian

    2013-01-01

    Full Text Available This study was designed to investigate the effect of long-term electroacupuncture at Baihui (DU20 and Zusanli (ST36 on cerebral microvessels and neurons in CA1 region of hippocampus in spontaneously hypertensive rats (SHR. A total of 45 male Wistar rats and 45 SHR were randomly grouped, with or without electroacupuncture (EA at DU20 and ST36, once every other day for a period of 8 weeks. The mean arterial pressure (MAP was measured once every 2 weeks. Cerebral blood flow (CBF and the number of open microvessels in hippocampal CA1 region were detected by Laser Doppler and immunohistochemistry, respectively. Nissl staining and Western blotting were performed, respectively, to determine hippocampus morphology and proteins that were implicated in the concerning signaling pathways. The results showed that the MAP in SHR increased linearly over the observation period and was significantly reduced following electroacupuncture as compared with sham control SHR rats, while no difference was observed in Wistar rats between EA and sham control. The CBF, learning and memory capacity, and capillary rarefaction of SHR were improved by EA. The upregulation of angiotensin II type I receptor (AT1R, endothelin receptor (ETAR, and endothelin-1 (ET-1 in SHR rats was attenuated by electroacupuncture, suggesting an implication of AT1R, ETAR, and ET-1 pathway in the effect of EA.

  13. Sex-Differences in Renal Expression of Selected Transporters and Transcription Factors in Lean and Obese Zucker Spontaneously Hypertensive Fatty Rats

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    Andrea Babelova

    2015-01-01

    Full Text Available The aim of this study was to identify sex-dependent expression of renal transporter mRNA in lean and obese Zucker spontaneously hypertensive fatty (ZSF1 rats and to investigate the interaction of the most altered transporter, organic anion transporter 2 (Oat2, with diabetes-relevant metabolites and drugs. Higher incidence of glomerulosclerosis, tubulointerstitial fibrosis, and protein casts in Bowman’s space and tubular lumen was detected by PAS staining in obese male compared to female ZSF1 rats. Real-time PCR on RNA isolated from kidney cortex revealed that Sglt1-2, Oat1-3, and Oct1 were higher expressed in kidneys of lean females. Oct2 and Mrp2 were higher expressed in obese males. Renal mRNA levels of transporters were reduced with diabetic nephropathy in females and the expression of transcription factors Hnf1β and Hnf4α in both sexes. The highest difference between lean and obese ZSF1 rats was found for Oat2. Therefore, we have tested the interaction of human OAT2 with various substances using tritium-labeled cGMP. Human OAT2 showed no interaction with diabetes-related metabolites, diabetic drugs, and ACE-inhibitors. However, OAT2-dependent uptake of cGMP was inhibited by furosemide. The strongly decreased expression of Oat2 and other transporters in female diabetic ZSF1 rats could possibly impair renal drug excretion, for example, of furosemide.

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

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    Mohammed Zubaerul Ferdaus

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

  15. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity.

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    Gustavo S Masson

    Full Text Available Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR. Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training and sedentary (S SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC, NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR, p38 MAPK and ERK1/2 expression (Western blotting, NF-κB content (electrophoretic mobility shift assay and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control showed increased mean arterial pressure (172±3 mmHg, pressure variability and heart rate (358±7 b/min, decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S. These responses were followed by increased vagal component of heart rate variability (1.9-fold and resting bradycardia (-13% at the 4th week, and, by reduced vasomotor component of pressure variability (-28% and decreased mean arterial pressure (-7% only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro

  16. Aortic depressor nerve stimulation does not impede the dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats.

    Science.gov (United States)

    Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

    2017-05-01

    Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY; n = 8) rats and spontaneously hypertensive rats (SHR; n = 7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, and 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4 ± 14.0 vs. 51.6 ± 11.3 arbitrary units in WKY, P = 0.012; and 248.7 ± 33.9 vs. 181.1 ± 16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8 ± 6.6 vs. 81.2 ± 5.4 mmHg in WKY, P = 0.004; and 128.6 ± 9.8 vs. 114.7 ± 10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55 ± 0.93 vs. 13.03 ± 1.28 dB/decade in WKY, P = 0.542; and 17.37 ± 1.01 vs. 17.47 ± 1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex. Copyright © 2017 the American Physiological Society.

  17. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity.

    Science.gov (United States)

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

    2014-01-01

    Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-κB content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172±3 mmHg), pressure variability and heart rate (358±7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (-13%) at the 4th week, and, by reduced vasomotor component of pressure variability (-28%) and decreased mean arterial pressure (-7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro

  18. Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

    2016-03-01

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men.

    Science.gov (United States)

    Dalmasso, Carolina; Patil, Chetan N; Yanes Cardozo, Licy L; Romero, Damian G; Maranon, Rodrigo O

    2017-10-17

    The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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

    Science.gov (United States)

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

    2013-02-01

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

  1. What is the optimal duration of middle-cerebral artery occlusion consistently resulting in isolated cortical selective neuronal loss in the spontaneously hypertensive rat?

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    Sohail eEjaz

    2015-03-01

    Full Text Available Introduction and Objectives: Selective neuronal loss (SNL in the reperfused penumbra may impact clinical recovery and is thus important to investigate. Brief proximal middle cerebral artery occlusion (MCAo results in predominantly striatal SNL, yet cortical damage is more relevant given its behavioral implications and that thrombolytic therapy mainly rescues the cortex. Distal temporary MCAo (tMCAo does target the cortex, but the optimal occlusion duration that results in isolated SNL has not been determined. In the present study we assessed different distal tMCAo durations looking for consistently pure SNL.Methods: Microclip distal tMCAo (md-tMCAo was performed in ~6-month old male spontaneously hypertensive rats (SHRs. We previously reported that 45min md-tMCAo in SHRs results in pan-necrosis in the majority of subjects. Accordingly, three shorter MCAo durations were investigated here in decremental succession, namely 30, 22 and 15mins (n=3, 3 and 7 subjects, respectively. Recanalization was confirmed by MR angiography just prior to brain collection at 28 days and T2-weighted MRI was obtained for characterization of ischemic lesions. NeuN, OX42 and GFAP immunohistochemistry appraised changes in neurons, microglia and astrocytes, respectively. Ischemic lesions were categorized into three main types: 1 pan-necrosis; 2 partial infarction; and 3 SNL. Results: Pan-necrosis or partial infarction was present in all 30min and 22min subjects, but not in the 15min group (p < 0.001, in which isolated cortical SNL was consistently present. MRI revealed characteristic hyperintense abnormalities in all rats with pan-necrosis or partial infarction, but no change in any 15min subject. Conclusions: We found that 15min distal MCAo consistently resulted in pure cortical SNL, whereas durations equal or longer than 22min consistently resulted in infarcts. This model may be of use to study the pathophysiology of cortical SNL and its prevention by appropriate

  2. Comparison of the validity of the use of the spontaneously hypertensive rat as a model of attention deficit hyperactivity disorder in males and females.

    Science.gov (United States)

    Bayless, Daniel W; Perez, Maria C; Daniel, Jill M

    2015-06-01

    The spontaneously hypertensive rat (SHR) is a commonly used and well-studied rodent model of attention deficit hyperactivity disorder (ADHD). Sex differences in the cognitive symptoms of ADHD are reported. However, the female SHR rat is much less studied than its male counterpart. The goal of the current study was to assess the validity of the SHR rodent model of ADHD by examining attentional performance, inhibitory control, and hyperactivity in both male and female SHR rats. Adult SHR and control Wistar-Kyoto rats were trained on the 5-choice serial reaction time task, a self-paced test of attention and inhibitory control. This task requires animals to identify the location of a brief light stimulus among five possible locations under several challenging conditions. Analyses of percent correct revealed that attentional performance in SHR females was not significantly different from control females, whereas attentional performance in SHR males was significantly different from control males. Analyses of the number of premature responses revealed that SHR rats made more inhibitory control errors than did control rats and that this decrease in inhibitory control was present in both SHR males and females. Analyses of activity in the open field revealed that SHR rats were more hyperactive than were control rats and that this increased hyperactivity was present in both SHR males and females. The current findings have implications for the study of sex differences in ADHD and for the use of SHR rats as a model of ADHD in females. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Transcriptome of the NTS in exercise-trained spontaneously hypertensive rats: implications for NTS function and plasticity in regulating blood pressure.

    Science.gov (United States)

    Waki, Hidefumi; Gouraud, Sabine S; Bhuiyan, Mohammad E R; Takagishi, Miwa; Yamazaki, Toshiya; Kohsaka, Akira; Maeda, Masanobu

    2013-01-07

    The nucleus tractus solitarii (NTS) controls the cardiovascular system during exercise, and alteration of its function may underlie exercise-induced cardiovascular adaptation. To understand the molecular basis of the NTS's plasticity in regulating blood pressure (BP) and its potential contribution to the antihypertensive effects, we characterized the gene expression profiles at the level of the NTS after long-term daily wheel running in spontaneously hypertensive rats (SHRs). Genome-wide microarray analysis was performed to screen for differentially expressed genes in the NTS between exercise-trained (12 wk) and control SHRs. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that daily exercise altered the expression levels of NTS genes that are functionally associated with metabolic pathways (5 genes), neuroactive ligand-receptor interactions (4 genes), cell adhesion molecules (3 genes), and cytokine-cytokine receptor interactions (3 genes). One of the genes that belonged to the neuroactive ligand-receptor interactions category was histamine receptor H(1). Since we confirmed that the pressor response induced by activation of this receptor is increased after long-term daily exercise, it is suggested that functional plasticity in the histaminergic system may mediate the facilitation of blood pressure control in response to exercise but may not be involved in the lowered basal BP level found in exercise-trained SHRs. Since abnormal inflammatory states in the NTS are known to be prohypertensive in SHRs, altered gene expression of the inflammatory molecules identified in this study may be related to the antihypertensive effects in exercise-trained SHRs, although such speculation awaits functional validation.

  4. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

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    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

  5. Chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in adult spontaneously hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD).

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    Pires, Vanessa A; Pamplona, Fabrício A; Pandolfo, Pablo; Prediger, Rui D S; Takahashi, Reinaldo N

    2010-12-20

    The spontaneously hypertensive rat (SHR) is frequently used as an experimental model for the study of attention deficit hyperactivity disorder (ADHD) since it displays behavioural and neurochemical features of ADHD. Increasing evidence suggests that caffeine might represent an important therapeutic tool for the treatment of ADHD and we recently demonstrated that the acute administration of caffeine improves several learning and memory impairments in adult SHR rats. Here we further evaluated the potential of caffeine in ADHD therapy. Female Wistar (WIS) and SHR rats were treated with caffeine (3mg/kg, i.p.) or methylphenidate (MPD, 2mg/kg, i.p.) for 14 consecutive days during the prepubertal period (post-natal days 25-38) and they were tested later in adulthood in the object-recognition task. WIS rats discriminated all the objects used, whereas SHR were not able to discriminate pairs of objects with subtle structural differences. Chronic treatment with caffeine or MPD improved the object-recognition deficits in SHR rats. Surprisingly, these treatments impaired the short-term object-recognition ability in adult WIS rats. The present drug effects are independent of changes in locomotor activity, arterial blood pressure and body weight in both rat strains. These findings suggest that chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in discriminative learning impairments of SHR, suggesting caffeine as an alternative therapeutic strategy for the early management of ADHD symptoms. Nevertheless, our results also emphasize the importance of a correct diagnosis and the caution in the use of stimulant drugs such as caffeine and MPD during neurodevelopment since they can disrupt discriminative learning in non-ADHD phenotypes. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  7. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Sung, Jin Young; Choi, Hyoung Chul

    2011-01-01

    Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

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

    Science.gov (United States)

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

    2017-03-05

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

  9. Spontaneous subdural hematoma associated to Duret hemorrhage

    Directory of Open Access Journals (Sweden)

    William Alves Martins, MD

    2015-03-01

    Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.

  10. A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    Gullberg, Grant, T; Huesman, Ronald, H; Reutter, Bryan, W; Sitek, Arkadiusz; Veress, Alexander, I; Weiss, Jeffrey, A; Yang, Yongfeng

    2017-06-13

    Problem: In the case of hypertrophy caused by pressure overload (hypertension) there is an increase in cardiac mass and modification cardiac metabolism. Aim: This study was designed to study the changes in glucose metabolism, ejection fraction, and deformation in the left ventricle with the progression of hypertrophy in spontaneous hypertensive rats (SHR). Methods: Dynamic PET data were acquired using the microPET II at UC Davis. Two rats were imaged at 10-week intervals for 18 months. Each time a dose of approximately 1- 1.5 mCi of F-18-FDG was injected into a normotensive Wistar Kyoto (WKY) rat and the same dose was injected into a SHR rat. Each rat was imaged using a gated dynamic acquisition for 80 minutes acquiring list mode data with cardiac gating of approximately 600-900 million total counts. For the analysis of glucose of metabolism, the list mode data were histogrammed into a dynamic sequence (42 frames over 80 mins). For each time frame, projection data of 1203 140x210 sinograms of 0.582 mm bins were formed by summing the last three gates before and one after the R-wave trigger to correspond to the diastolic phase of the cardiac cycle. Dynamic sequences of 128x128x83 matrices of 0.4x0.4x0.582 mm3 voxels in x, y, and z were reconstructed using an iterative MAP reconstruction which used a prior that penalized the high frequency components of the reconstruction using appropriate weighting between 26 nearest neighboring voxels. Time activity curves were generated from the dynamic reconstructed sequence for the blood and left ventricular tissue regions of interest which were fit to a 2-compartment model to obtain a least squares fit for the kinetic parameters. For the analysis of deformation, the list mode data were histogrammed into 8 gates of the cardiac cycle, each gate was the total sum of the later 60 mins of the 80 min acquisition. Images of 128x128x83 matrices for each gate were reconstructed using the same iterative MAP reconstruction used to

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

    Science.gov (United States)

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

    2014-05-16

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

  12. Combined treatment with a β3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Suzuki, Toshiro; Saito, Tetsuichi; Yokoyama, Hitoshi; Nakazawa, Masaki; Ishizuka, Osamu

    2017-04-01

    This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the β 3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the β 3 -ARs and M 3 -MRs expressed within the urinary bladders were analyzed. Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M 3 -MR and β 3 -AR mRNA. The tissue distribution of M 3 -MRs was similar to that of the β 3 -ARs. This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

  13. Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

    Science.gov (United States)

    2014-01-01

    Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a behavioral disorder affecting 3-5% of children. Although ADHD is highly heritable, environmental factors like exposure during early development to various toxic substances like polychlorinated biphenyls (PCBs) may contribute to the prevalence. PCBs are a group of chemical industrial compounds with adverse effects on neurobiological and cognitive functioning, and may produce behavioral impairments that share significant similarities with ADHD. The present study examined the relation between exposure to PCB 153 and changes in ADHD-like behavior in an animal model of ADHD, the spontaneously hypertensive rats (SHR/NCrl), and in Wistar Kyoto (WKY/NHsd) controls. Methods SHR/NCrl and WKY/NHsd, males and females, were orally given PCB 153 dissolved in corn oil at around postnatal day (PND) 8, 14, and 20 at a dosage of 1, 3 or 6 mg/kg bodyweight at each exposure. The control groups were orally administered corn oil only. The animals were behaviorally tested for exposure effects from PND 37 to 64 using an operant procedure. Results Exposure to PCB 153 was associated with pronounced and long-lasting behavioral changes in SHR/NCrl. Exposure effects in the SHR/NCrl depended on dose, where 1 mg/kg tended to reduce ADHD-like behaviors and produce opposite behavioral effects compared to 3 mg/kg and 6 mg/kg, especially in the females. In the WKY/NHsd controls and for the three doses tested, PCB 153 exposure produced a few specific behavioral changes only in males. The data suggest that PCB 153 exposure interacts with strain and sex, and also indicate a non-linear dose–response relation for the behaviors observed. Conclusions Exposure to PCB 153 seems to interact with several variables including strain, sex, dose, and time of testing. To the extent that the present findings can be generalized to humans, exposure effects of PCB 153 on ADHD behavior depends on amount of exposure, where high doses may aggravate ADHD

  14. Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Baskin, Britahny M; Dwoskin, Linda P; Kantak, Kathleen M

    2015-04-01

    Past research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder showed that adolescent methylphenidate treatment enhanced cocaine abuse risk in SHR during adulthood. The acquisition of cocaine self-administration was faster, and cocaine dose-response functions were shifted upward under fixed-ratio and progressive ratio schedules compared to adult SHR that received adolescent vehicle treatment or to control strains that received adolescent methylphenidate treatment. The current study determined if extending treatment beyond adolescence would ameliorate long-term consequences of adolescent methylphenidate treatment on cocaine abuse risk in adult SHR. Treatments (vehicle or 1.5mg/kg/day oral methylphenidate) began on postnatal day 28. Groups of male SHR were treated with vehicle during adolescence and adulthood, with methylphenidate during adolescence and vehicle during adulthood, or with methylphenidate during adolescence and adulthood. The group receiving adolescent-only methylphenidate was switched to vehicle on P56. Cocaine self-administration began on postnatal day 77, and groups receiving methylphenidate during adolescence and adulthood were treated either 1-h before or 1-h after daily sessions. At baseline under a fixed-ratio 1 schedule, cocaine self-administration (2h sessions; 0.3mg/kg unit dose) did not differ among the four treatment groups. Under a progressive ratio schedule (4.5h maximum session length; 0.01-1.0mg/kg unit doses), breakpoints for self-administered cocaine in SHR receiving the adult methylphenidate treatment 1-h pre-session were not different from the vehicle control group. However, compared to the vehicle control group, breakpoints for self-administered cocaine at the 0.3 and 1.0mg/kg unit doses were greater in adult SHR that received adolescent-only methylphenidate or received methylphenidate that was continued into adulthood and administered 1-h post-session. These findings suggest that

  15. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China (China); Chonan, Ritsu [Koei Kogyo Co., Ltd., Tokyo, 101-0063 Japan (Japan); Yamahara, Johji [Pharmafood Institute, Kyoto, 602-8136 Japan (Japan); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 China (China); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000 Australia (Australia)

    2014-10-15

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  16. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    International Nuclear Information System (INIS)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-01-01

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  17. Amlodipine and atorvastatin improved hypertensive cardiac hypertrophy through regulation of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin system in spontaneous hypertension rats.

    Science.gov (United States)

    Lu, Jingchao; Liu, Fan; Liu, Demin; Du, Hong; Hao, Jie; Yang, Xiuchun; Cui, Wei

    2016-06-01

    The present study aims to study the role of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin (RANKL/RANK/OPG) system in cardiac hypertrophy in a spontaneous hypertension rat (SHR) model and the effects of amlodipine and atorvastatin intervention. Thirty-six-week-old male SHRs were randomly divided into four groups: 1) SHR control group; 2) amlodipine alone (10 mg/kg/d) group, 3) atorvastatin alone (10 mg/kg/d) group, 4) combination of amlodinpine and atorvastatin (10 mg/kg/d for each) group. Same gender, weight, and age of Wistar-Kyoto (WKY) rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The thicknesses of left ventricle walls, left ventricle weight, and cardiac function were measured by transthoracic echocardiography. Left ventricular pressure and function were assessed by hemodynamic examination. Cardiomyocyte hypertrophy and collagen accumulation in cardiac tissue were measured by hematoxylin and eosin (HE) and Masson staining, respectively. The hydroxyproline content of cardiac tissue was examined by biochemistry technique. RANKL, RANK and OPG mRNA, protein expression and tissue localization were studied by RT-PCR, Immunohistochemistry and Western blot. Treatment with amlodipine or atorvastatin alone significantly decreased left ventricular mass index, cardiomyocyte cross-sectional area and interstitial fibrosis in SHR (each P < 0.05). Moreover, combined amlodipine and atorvastatin treatment induced significant reversal of left ventricular hypertrophy and decreased cardiomyocyte cross-sectional area and interstitial fibrosis in SHR to a greater extent than each agent alone (P < 0.05). Compared with WKY rats, the myocardial expression of RANKL, RANK, and OPG was increased. Both amlodipine and atorvastatin reduced RANKL, RANK, and OPG expression, with the best effects seen with the combination. Based on our results

  18. Effects of captopril treatment on augmented norepinephrine-stimulated calcium entry through voltage-dependent calcium channels in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Paulis, Ĺudovít; Dobešová, Zdenka; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S4 (2006), S338-S338 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] R&D Projects: GA MZd(CZ) NR7786 Keywords : voltage-dependent calcium channel * hypertension * captopril * norepinephrine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  19. Subclinical hyperthyroidism (Sh) in atomic-bomb survivors in Japan

    International Nuclear Information System (INIS)

    Ashizawa, K.; Imaizumi, M.; Usa, T.; Tominaga, T.; Hida, A.; Ejima, E.; Neriishi, K.; Soda, M.; Fujiwara, S.; Maeda, R.; Akahoshi, M.; Nagataki, S.; Eguchi, K.

    2005-01-01

    Full text: Purpose/Background Subclinical hyperthyroidism (Sh) is defined as a biochemical abnormality characterized by a subnormal level of TSH with otherwise normal thyroid tests (F T 3 , F T 4 ) and no clinical symptoms. There are only a small number of cross-sectional studies on the prevalence of Sh. With the improvement of the sensitivity of TSH assay, it has become possible to survey the clinical significance of Sh. With regard to both Sh and subclinical hypothyroidism, discussions are being focused on such as the necessity of treatment. In order to elucidate the clinical significance of Sh, examination data of A-bomb survivors in Hiroshima and Nagasaki were analyzed. Subjects and Method Between 2000 and 2003, of 4,090 A-bomb survivors (1,352 males and 2,738 females with average age of 70.7), 75 individuals (1.83%) with Sh were found who had normal Free T 4 (0.71∼1.51 ng/dL) and TSH<0.45 m U/L. Analysis was limited to those who had not taken antithyroid drugs or thyroxin, and the Sh group (n=35; 9 males and 26 females) was compared with a control group with TSH:0.45∼4.5 m U/L (Group C; N=3,243; 1,109 males and 2,134 females). Result: Nine individuals had TSH<0.1 m U/L. In the Sh group, six individuals were TPO antibody-positive (17%) and 14 were TG antibody-positive (40%); hence, TG antibody-positive was significantly greater in number (p=0.0096). Hematological biochemical tests showed no significant difference between the two groups. Electrocardiograms indicated that more individuals had atrial fibrillation [p=0.028; Odds ratio (OR)=3.98; 95% Confidential interval (CI)=1.2-13.7] or ventricular premature contraction [p=0.016; OR=3.29; 95% CI=1.3-8.6] in the Sh group. In terms of the presence or absence of diabetes, dyslipidemia, hypertension, and hyperuricemia, there was no difference between the two groups. One individual from the Sh group was confirmed to have Graves' disease two years later. Conclusion: Since more individuals in the Sh group were

  20. Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats Efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensas

    Directory of Open Access Journals (Sweden)

    José Ricardo Sousa Ayres de Moura

    2006-08-01

    Full Text Available PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR. METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1. Pregnancy was confirmed by sperm-positive vaginal smear (Day 0. Wistar-EPM-1 rats served as counterpart control (C-1. SHR rats were randomized in 4 groups (n=10: Group Control 2, non-treated rats; Group L-Arginine treated with L-arginine 2%; Group Alpha-methyldopa treated with Alpha-methyldopa 33mg/Kg; Group L-Arginine+Alpha-methyldopa treated with L-arginine 2%+Alpha-methyldopa 33mg/Kg. L-arginine 2% solution was offered ad libitum in drinking water and Alpha-methyldopa was administered by gavage twice a day during the length of pregnancy (20 days. Blood pressure was measured by tailcuff plethysmography on days 0 and 20. Body weight was measured on days 0, 10 and 20. Results were expressed as mean ± SD (Standard Deviation. One-Way ANOVA/Tukey (or Kruskal-Wallis/Dunn, as appropriate was used for group comparisons. Statistical significance was accepted as pOBJETIVO: Avaliar os efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensivas (SHR. MÉTODOS: 30 SHR e 10 Wistar-EPM-1 ratas virgens foram utilizadas no estudo. Antes da distribuição, as fêmeas foram acasaladas com machos da mesma linhagem (3:1; a prenhez foi confirmada pela presença de espermatozóides no esfregaço vaginal. As ratas Wistar-EPM-1 foram utilizadas como controles. As ratas SHR foram aleatoriamente distribuídas em 4 grupos (n=10: Grupo Controle-2, não-tratado; Grupo L-Arginina, tratado com L-arginina; Grupo Alfa-metildopa, tratado com alfa-metildopa; Grupo L-Arginina+Alfa-metildopa, tratado com arginina+Alfa-metildopa. L-arginina (2% foi oferecida ad libitum na água de beber e a Alfa-metildopa (33 mg/Kg foi administrada por gavagem, duas vezes ao dia, durante toda a

  1. Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

    2016-05-01

    We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  3. Augmented norepinephrine-stimulated Ca2+ entry via voltage-dependent Ca2+ channels in spontaneously hypertensive rats (SHR): effects of captopril treatment

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Dobešová, Zdenka; Paulis, L.; Kuneš, Jaroslav

    2006-01-01

    Roč. 22, č. 13 (2006), s. 58-58 ISSN 1000-4718. [International Congress of Pathophysiology /5./. 28.06.2006-01.07.2006, Beijing] R&D Projects: GA MZd(CZ) NR7786 Keywords : Ca2+ entry * voltage-dependent Ca2+ channels * hypertensive rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  4. Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T

    2012-01-01

    BACKGROUND: Endothelin-1 (ET1) is a potent vasoconstrictor peptide with pro-mitogenic and pro-inflammatory properties and is therefore of interest in the development of endothelial dysfunction, endothelium-dependent flow-related remodeling, and hypertension-related remodeling. ET1 can be formed t...

  5. The expression of neuronal nitric oxide synthase (NNOS) in brainstem and cerebellum of spontaneously hypertensive rats (SHR): The effect of chronic captopril treatment

    Czech Academy of Sciences Publication Activity Database

    Hojná, Silvie; Dobešová, Zdenka; Zicha, Josef; Kuneš, Jaroslav

    2005-01-01

    Roč. 46, č. 4 (2005), s. 895-895 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] R&D Projects: GA ČR(CZ) GA305/03/0769 Keywords : nitric oxide synthase * brain * captopril * hypertension Subject RIV: ED - Physiology

  6. Diesel exhaust induced pulmonary and cardiovascular impairment: The role of hypertension intervention

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Thomas, Ronald F.; Ledbetter, Allen D.; Schladweiler, Mette C.; Bass, Virginia; Krantz, Q. Todd; King, Charly [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Nyska, Abraham [Tel Aviv University, Tel Aviv (Israel); Richards, Judy E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Andrews, Debora [Research Core Unit, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC 27711 (United States); Gilmour, M. Ian [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States)

    2013-04-15

    Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or L-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500 μg/m{sup 3}), 4 h/day for 2 days or 5 days/week for 4 weeks. Acute and 4-week gas and DE exposures increased neutrophils and γ-glutamyl transferase (γ-GT) activity in lavage fluid of WKY and SH rats. DE (4 weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-α, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while L-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF γ-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by L-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-α, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers. - Highlights: ► Acute diesel exhaust exposure induces pulmonary inflammation in healthy rats. ► In hypertensive rats diesel exhaust effects are seen only after long term exposure. ► Normalizing blood pressure reverses lung protein leakage caused by diesel exhaust. ► Normalizing blood pressure reverses

  7. Effect of 1,25(OH)2 vitamin D3 and ionized Ca2+ on 45Ca uptake by primary cultures of aortic myocytes of spontaneously hypertensive and Wistar Kyoto normotensive rats

    International Nuclear Information System (INIS)

    Bukoski, R.D.; Xue, H.; McCarron, D.A.

    1987-01-01

    The effect of several regulators of whole animal Ca 2+ homeostasis on 45 Ca uptake by primary cultures of aortic myocytes isolated from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats was examined. Exposure of confluent cells to 1.0, 1.25 or 1.50 mM ionized Ca 2+ in serum-free medium for seven days resulted in increased 45 Ca uptake at the higher concentrations of Ca 2+ in cells of the SHR but not the WKY. 1,25 (OH)2 vitamin D3 (1 ng/ml) for 7 days caused enhanced influx in cells from both the SHR and WKY while parathyroid hormone (1-34) (1 ng/ml) was without effect. The data indicate that humoral factors that serve to regulate whole animal Ca 2+ homeostasis may also play a role in the regulation of Ca 2+ metabolism of the vascular smooth muscle cell

  8. Spontaneous, L-Arginine-Induced and Spironolactone-Induced Regression of Protein Remodeling of the Left Ventricle in L-NAME-Induced Hypertension

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Potáčová, A.; Pelouch, V.; Paulis, L.; Matúšková, J.; Krajčírovičová, K.; Pecháňová, Olga; Adamcová, M.

    2007-01-01

    Roč. 56, Suppl.2 (2007), S55-S62 ISSN 0862-8408 Grant - others:VEGA(SK) 1/3429/06; VEGA(SK) 2/6148/26; -(SK) APVT-51-027404 Institutional research plan: CEZ:AV0Z50110509 Keywords : spironolactone * regression of hypertrophy * L-NAME hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

  9. Glucagon‐like peptide‐1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP‐1 receptors

    OpenAIRE

    Ronn, Jonas; Jensen, Elisa P.; Wewer Albrechtsen, Nicolai J.; Holst, Jens Juul; Sorensen, Charlotte M.

    2017-01-01

    Abstract Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone increasing postprandial insulin release. GLP‐1 also induces diuresis and natriuresis in humans and rodents. The GLP‐1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP‐1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP‐1 has been reported both to increase and decrease MAP. The aim of this study was to ...

  10. Nine novel angiotensin I-converting enzyme (ACE) inhibitory peptides from cuttlefish (Sepia officinalis) muscle protein hydrolysates and antihypertensive effect of the potent active peptide in spontaneously hypertensive rats.

    Science.gov (United States)

    Balti, Rafik; Bougatef, Ali; Sila, Assaâd; Guillochon, Didier; Dhulster, Pascal; Nedjar-Arroume, Naima

    2015-03-01

    This study aimed to identify novel ACE inhibitory peptides from the muscle of cuttlefish. Proteins were hydrolyzed and the hydrolysates were then subjected to various types of chromatography to isolate the active peptides. Nine ACE inhibitory peptides were isolated and their molecular masses and amino acid sequences were determined using ESI-MS and ESI-MS/MS, respectively. The structures of the most potent peptides were identified as Val-Glu-Leu-Tyr-Pro, Ala-Phe-Val-Gly-Tyr-Val-Leu-Pro and Glu-Lys-Ser-Tyr-Glu-Leu-Pro. The first peptide displayed the highest ACE inhibitory activity with an IC50 of 5.22μM. Lineweaver-Burk plots suggest that Val-Glu-Leu-Tyr-Pro acts as a non-competitive inhibitor against ACE. Furthermore, antihypertensive effects in spontaneously hypertensive rats (SHR) also revealed that oral administration of Val-Glu-Leu-Tyr-Pro can decrease systolic blood pressure significantly (p<0.01). These results suggest that the Val-Glu-Leu-Tyr-Pro would be a beneficial ingredient for nutraceuticals and pharmaceuticals acting against hypertension and its related diseases. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  11. Salsalate ameliorates metabolic disturbances by reducing inflammation in spontaneously hypertensive rats expressing human C-reactive protein and by activating brown adipose tissue in nontransgenic controls

    Czech Academy of Sciences Publication Activity Database

    Trnovská, J.; Šilhavý, Jan; Kuda, Ondřej; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Škop, V.; Oliyarnyk, O.; Kazdová, L.; Haluzík, M.; Pravenec, Michal

    2017-01-01

    Roč. 12, č. 6 (2017), č. článku e0179063. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * insulin resistance * C-reactive protein * spintaneously hypertensive rat * salsalate Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Endocrinology and metabolism (including diabetes, hormones); Endocrinology and metabolism (including diabetes, hormones) (UMG-J) Impact factor: 2.806, year: 2016

  12. Potential of a renin inhibitory peptide from the red seaweed Palmaria palmata as a functional food ingredient following confirmation and characterization of a hypotensive effect in spontaneously hypertensive rats.

    Science.gov (United States)

    Fitzgerald, Ciaran; Aluko, Rotimi E; Hossain, Mohammad; Rai, Dilip K; Hayes, Maria

    2014-08-20

    This work examined the resistance of the renin inhibitory, tridecapeptide IRLIIVLMPILMA derived previously from a Palmaria palmata papain hydrolysate, during gastrointestinal (GI) transit. Following simulated GI digestion, breakdown products were identified using mass spectrometry analysis and the known renin and angiotensin I converting enzyme inhibitory dipeptide IR was identified. In vivo animal studies using spontaneously hypertensive rats (SHRs) were used to confirm the antihypertensive effects of both the tridecapeptide IRLIIVLMPILMA and the seaweed protein hydrolysate from which this peptide was isolated. After 24 h, the SHR group fed the P. palmata protein hydrolysate recorded a drop of 34 mm Hg in systolic blood pressure (SBP) from 187 (±0.25) to 153 (± 0.64) mm Hg SBP, while the group fed the tridecapeptide IRLIIVLMPLIMA presented a drop of 33 mm Hg in blood pressure from 187 (±0.95) to 154 (±0.94) mm Hg SBP compared to the SBP recorded at time zero. The results of this study indicate that the seaweed protein derived hydrolysate has potential for use as antihypertensive agents and that the tridecapeptide is cleaved and activated to the dipeptide IR when it travels through the GI tract. Both the hydrolysate and peptide reduced SHR blood pressure when administered orally over a 24 h period.

  13. Metabolic Modulation by Medium-Chain Triglycerides Reduces Oxidative Stress and Ameliorates CD36-Mediated Cardiac Remodeling in Spontaneously Hypertensive Rat in the Initial and Established Stages of Hypertrophy.

    Science.gov (United States)

    Saifudeen, Ismael; Subhadra, Lakshmi; Konnottil, Remani; Nair, R Renuka

    2017-03-01

    Left ventricular hypertrophy (LVH) is characterized by a decrease in oxidation of long-chain fatty acids, possibly mediated by reduced expression of the cell-surface protein cluster of differentiation 36 (CD36). Spontaneously hypertensive rats (SHRs) were therefore supplemented with medium-chain triglycerides (MCT), a substrate that bypasses CD36, based on the assumption that the metabolic modulation will ameliorate ventricular remodeling. The diet of 2-month-old and 6-month-old SHRs was supplemented with 5% MCT (Tricaprylin), for 4 months. Metabolic modulation was assessed by mRNA expression of peroxisome proliferator-activated receptor α and medium-chain acyl-CoA dehydrogenase. Blood pressure was measured noninvasively. LVH was assessed with the use of hypertrophy index, cardiomyocyte cross-sectional area, mRNA expression of B-type natriuretic peptide, cardiac fibrosis, and calcineurin-A levels. Oxidative stress indicators (cardiac malondialdehyde, protein carbonyl, and 3-nitrotyrosine levels), myocardial energy level (ATP, phosphocreatine), and lipid profile were determined. Supplementation of MCT stimulated fatty acid oxidation in animals of both age groups, reduced hypertrophy and oxidative stress along with the maintenance of energy level. Blood pressure, body weight, and lipid profile were unaffected by the treatment. The results indicate that modulation of myocardial fatty acid metabolism by MCT prevents progressive cardiac remodeling in SHRs, possibly by maintenance of energy level and decrease in oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Ocular Hypertension

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Ocular Hypertension Sections What Is Ocular Hypertension? Ocular Hypertension Causes ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Leer en Español: ¿Qué es la hipertensión ocular? ...

  15. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  16. The prevalence of resistant arterial hypertension and secondary causes in a cohort of hypertensive patients: a single center experience

    Directory of Open Access Journals (Sweden)

    Luigi Petramala

    2017-11-01

    Full Text Available The prevalence of resistant hypertension (RHT still remains unknown. Aim of the study was to investigate in a large cohort of hypertensive patients the prevalence of RHT, and to identify in these patients the secondary forms of arterial hypertension (SH. We enrolled a series of 3685 consecutive hypertensive patients. All patients underwent complete physical examination, laboratory tests, screening for SH. Ambulatory blood pressure monitoring (ABPM was performed to exclude white-coat hypertension. Further, we investigated for any obstructive sleep apnea syndrome (OSA. Only 232 (5.8% hypertensive patients fulfilled criteria for RHT. 91 (39% had a SH; 56 (61% hypertensive patients had a primary aldosteronism, 22 (24% had OSA, 7 (7.7% had a hypercortisolism, and 5 (5.5% had a renovascular hypertension (RVH. Only one patient had adrenal pheochromocytoma. An accurate definition and investigation into RHT is needed. We recommend ABPM to all patients at diagnosis. Finally, all patients must be screened for SH, such as adrenal hypertension, OSA and RVH, especially those who are apparently resistant to polypharmacological treatment.

  17. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    Takahashi R.N.

    2001-01-01

    Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

  18. Dissociation between spontaneously hypertensive (SHR) andWistar–Kyoto (WKY) rats in baseline performance and methylphenidate response on measures of attention, impulsivity and hyperactivity in a Visual Stimulus Position Discrimination Task

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.

    2009-10-08

    The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at three different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.

  19. Application of the biosurfactants produced by Bacillus spp. (SH 20 ...

    African Journals Online (AJOL)

    Application of the biosurfactants produced by Bacillus spp. (SH 20 and SH 26) and P. aeruginosa SH 29 isolated from the rhizosphere soil of an Egyptian salt marsh plant for the cleaning of oil - contaminataed vessels and enhancing the biodegradat.

  20. Inhibition and Promotion of Pyrolysis by Hydrogen Sulfide (H2S) and Sulfanyl Radical (SH)

    DEFF Research Database (Denmark)

    Zeng, Zhe; Altarawneh, Mohammednoor; Oluwoye, Ibukun

    2016-01-01

    the weakest C–H sites in alkenes and alkynes, except for ethylene, appears noticeably exothermic. Furthermore, abstraction of H from propene, 1-butene, and iso-butene displays pronounced spontaneity (i.e., ΔrG° hydrogen bond. However......, an alkyl radical readily abstracts H atom from H2S, with H2S acting as a potent scavenger for alkyl radicals in combustion processes. That is, these reactions proceed in the opposite direction than those involving SH and alkene or alkyne species, exhibiting shallow barriers and strong spontaneity. Our...... findings demonstrate that the documented inhibition effect of hydrogen sulfide (H2S) on pyrolysis of alkanes does not apply to alkenes and alkynes. During interaction with hydrocarbons, the inhibitive effect of H2S and promoting interaction of SH radical depend on the reversibility of the H abstraction...

  1. Análisis ecocardiográfico de la geometría ventricular izquierda en ratas espontáneamente hipertensas Echocardiographic study of left ventricular geometry the in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Eduardo M. Escudero

    2009-06-01

    Full Text Available El presente trabajo fue diseñado para analizar ecocardiográficamente la geometría del ventrículo izquierdo en ratas espontáneamente hipertensas (SHR. Se estudiaron 114 ratas macho de 4 meses de edad, 73 SHR y 41 Wistar (W a las que se les registró la presión arterial, la frecuencia cardíaca y se les realizó un ecocardiograma. Con las mediciones de diámetros y espesores de la pared ventricular izquierda se calcularon el espesor parietal relativo (h/r, el índice de masa del ventrículo izquierdo (IMVI, el volumen minuto, y el acortamiento medio ventricular. La geometría ventricular izquierda normal fue definida analizando el grupo de ratas normotensas y fijando los límites de IMVI y h/r a partir de la media más 2 desvíos estándar. Los patrones de geometría anormal se definieron como: remodelado concéntrico (RC: IMVI 0.71; hipertrofia excéntrica (HE: IMVI>2.06 mg/g - h/r 2.06 mg/g - h/r > 0.71. La presión arterial sistólica y el volumen minuto se utilizaron para estimar la resistencia periférica total (RPT. Doce por ciento de SHR presentaron geometría ventricular izquierda normal; 18% RC; 33% HC y 37% HE. El RC mostró el volumen latido más pequeño y la RPT más alta de cualquier grupo. HE presentó presión arterial sistólica similar a la de los otros grupos de SHR, volumen latido más alto y la RPT más baja. Estos hallazgos en SHR exhibiendo diferentes patrones de geometría ventricular izquierda, similares a los referidos en humanos, intensifican las similitudes entre la hipertensión esencial humana y las SHR.The purpose of this study was to analyze by echocardiogram left ventricular (LV geometry in spontaneously hypertensive rats (SHR. Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W. Left ventricular mass index (LVMI, relative wall thickness (RWT, stroke volume, and mid ventricular shortening were calculated with echocardiographic

  2. Model SH intelligent instrument for thickness measuring

    International Nuclear Information System (INIS)

    Liu Juntao; Jia Weizhuang; Zhao Yunlong

    1995-01-01

    The authors introduce Model SH Intelligent Instrument for thickness measuring by using principle of beta back-scattering and its application range, features, principle of operation, system design, calibration and specifications

  3. Chemical shift assignments of the partially deuterated Fyn SH2-SH3 domain.

    Science.gov (United States)

    Kieken, Fabien; Loth, Karine; van Nuland, Nico; Tompa, Peter; Lenaerts, Tom

    2018-04-01

    Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1 H, 15 N and 13 C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains. The BMRB accession number is 27165.

  4. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  5. Orexin, cardio-respiratory function, and hypertension

    OpenAIRE

    Li, Aihua; Nattie, Eugene

    2014-01-01

    In this review we focus on the role of orexin in cardio-respiratory functions and its potential link to hypertension. (1) Orexin, cardiovascular function, and hypertension. In normal rats, central administration of orexin can induce significant increases in arterial blood pressure (ABP) and sympathetic nerve activity (SNA), which can be blocked by orexin receptor antagonists. In spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can significantly lower blood pressure under ...

  6. Hypertensive Crisis

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Hypertensive Crisis: When You Should Call 9-1-1 for ... the Facts About HBP • Know Your Numbers Introduction Hypertensive Crisis Monitoring Your Blood Pressure At Home • Understand Symptoms ...

  7. Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats Estudo da bioequivalência de quatro diferentes marcas comerciais de maleato de enalapril em ratos espontaneamente hipertensos

    Directory of Open Access Journals (Sweden)

    Nilo César do Vale Baracho

    2008-04-01

    Full Text Available INTRODUCTION: High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. PURPOSE: To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR. METHODS: Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. RESULTS: The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. CONCLUSION: The use of generic drug and similars (A and B drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.INTRODUÇÃO: A hipertensão arterial é uma doença sistêmica que traz grandes repercussões clínicas e psico-sociais, cursa com uma elevada morbi-mortalidade e gera elevados gastos para o sistema de saúde. Seu tratamento envolve a utilização de fármacos anti-hipertensivos, os quais são comercializados como remédios de marca, genéricos ou similares. PURPOSE: Verificar o efeito anti-hipertensivo produzido por dose igualitária de diferentes marcas de maleato de enalapril, em ratos naturalmente hipertensos. MÉTODOS: Foram administrados, por meio de gavagem, 15 mg/kg de maleato de enalapril em 50 ratos naturalmente hipertensos e verificada a pressão arterial, através de pletismografia de cauda, a cada três dias, em um período de 16 dias. RESULTADOS

  8. Diuretic action of exogenous hydrogen sulfide in spontaneously ...

    African Journals Online (AJOL)

    Diuretic action of exogenous hydrogen sulfide in spontaneously hypertensive diabetic rats. F ud Din Ahmad, MA Sattar, HA Rathore, S Akhter, O Hui Jin, EJ Johns. Abstract. Purpose: To examine the hypothesis that in hypertensive diabetic rats hydrogen sulphide (H2S) reduces blood pressure through diuretic action in ...

  9. Resistant Hypertension.

    Science.gov (United States)

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  10. Volume quantification of acute infratentorial hemorrhage with computed tomography: validation of the formula 1/2ABC and 2/3SH.

    Directory of Open Access Journals (Sweden)

    Wanlin Yang

    Full Text Available OBJECTIVE: To compare the accuracy of formula 1/2ABC with 2/3SH on volume estimation for hypertensive infratentorial hematoma. METHODS: One hundred and forty-seven CT scans diagnosed as hypertensive infratentorial hemorrhage were reviewed. Based on the shape, hematomas were categorized as regular or irregular. Multilobular was defined as a special shape of irregular. Hematoma volume was calculated employing computer-assisted volumetric analysis (CAVA, 1/2ABC and 2/3SH, respectively. RESULTS: The correlation coefficients between 1/2ABC (or 2/3SH and CAVA were greater than 0.900 in all subgroups. There were neither significant differences in absolute values of volume deviation nor percentage deviation between 1/2ABC and 2/3SH for regular hemorrhage (P>0.05. While for cerebellar, brainstem and irregular hemorrhages, the absolute values of volume deviation and percentage deviation by formula 1/2ABC were greater than 2/3SH (P<0.05. 1/2ABC and 2/3SH underestimated hematoma volume each by 10% and 5% for cerebellar hemorrhage, 14% and 9% for brainstem hemorrhage, 19% and 16% for regular hemorrhage, 9% and 3% for irregular hemorrhage, respectively. In addition, for the multilobular hemorrhage, 1/2ABC underestimated the volume by 9% while 2/3SH overestimated it by 2%. CONCLUSIONS: For regular hemorrhage volume calculation, the accuracy of 2/3SH is similar to 1/2ABC. While for cerebellar, brainstem or irregular hemorrhages (including multilobular, 2/3SH is more accurate than 1/2ABC.

  11. Mineralocorticoid hypertension

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Hypertension affects about 10 - 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta, aldosterone-producing pathologies (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and 3, non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH syndrome, congenitalvadrenal hyperplasia, and drugs with mineraocorticoid activity (locorice, carbenoxole therapy to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics. Direct aldosterone synthetase antagonists represent a promising future therapy.

  12. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    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.

  13. Influência da suplementação de creatina sobre a massa óssea de ratos espontaneamente hipertensos Influence of creatine supplementation on bone mass of spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Christiano Robles Rodrigues Alves

    2012-06-01

    Full Text Available INTRODUÇÃO: Recentes evidências indicam que a suplementação de creatina (Cr é capaz de aumentar a densidade mineral óssea (DMO no fêmur de ratos saudáveis em crescimento. Entretanto, há poucos estudos que testam a efetividade da suplementação desse nutriente em condições de perda óssea. OBJETIVO: Investigar o efeito da suplementação de Cr na DMO e no conteúdo mineral ósseo (CMO de ratos espontaneamente hipertensos (SHR, um modelo experimental de baixa massa óssea. MATERIAIS E MÉTODOS: Dezesseis ratos SHR machos com 8 meses de idade foram randomizados em dois grupos experimentais pareados pelo peso corporal, a saber: 1 Pl: SHR tratados com placebo (água destilada; n = 8; e 2 Cr: SHR tratados com Cr (n = 8. Após nove semanas de suplementação os animais foram eutanasiados e o fêmur e a coluna vertebral (L1-L4 foram analisados por densitometria óssea (Dual Energy X-Ray Absorptiometry. RESULTADOS: Não houve diferença significativa na DMO (Pl = 0,249 ± 0,003 g/cm² vs. Cr = 0,249 ± 0,004 g/cm²; P = 0,95 e no CMO (Pl = 0,509 ± 0,150 g vs. Cr = 0,509 ± 0,017 g; P = 0,99 da coluna vertebral e na DMO (Pl = 0,210 ± 0,004 g/cm² vs. Cr = 0,206 ± 0,004 g/cm2;P = 0,49 e no CMO (Pl = 0,407 ± 0,021 g vs. Cr = 0,385 ± 0,021 g; P = 0,46 do fêmur total entre os grupos experimentais. CONCLUSÃO: Neste estudo, usando um modelo experimental de baixa massa óssea, a suplementação de Cr não afetou a massa óssea.INTRODUCTION: Recent evidence has suggested that creatine supplementation (Cr can increase the bone mineral density (BMD of the femur in healthy growing rats. Nevertheless, studies assessing the efficacy of the Cr supplementation in conditions characterized by bone mass loss are scarce. OBJECTIVE: To investigate the effect of Cr supplementation on BMD and bone mineral content (BMC in spontaneously hypertensive rats (SHRs, an experimental model of osteoporosis. MATERIALS AND METHODS: Sixteen 8-month-old male SHRs were

  14. Temporality in Manyōshū

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    Yamaguchi Toshiko

    2016-12-01

    Full Text Available Using the Manyōshū corpus, the paper argues that conceptual metaphor theory imposes limitations on the diversity of linguistic facts, particularly those concerning the speaker or the poet who is communicating. The paper offers explanations of the nature of time by drawing upon the inference operating within “basic sign structure”, specifically, indexicality and iconicity, both of which are at the heart of human semiotic activity.

  15. Differences in emotion processing in patients with essential and secondary hypertension.

    Science.gov (United States)

    Consoli, Silla M; Lemogne, Cédric; Roch, Bernard; Laurent, Stéphane; Plouin, Pierre-François; Lane, Richard D

    2010-05-01

    An impaired ability to experience and express emotions, known as alexithymia, has previously been associated with hypertension. Alexithymia and related emotion-processing variables, however, have never been examined as a function of the type of hypertension, essential (EH) or secondary (SH). Our working hypothesis was that if dysregulated emotional processes play a key neurobiological role in EH, they would be less present in hypertension due to specific medical causes or SH. A total of 98 consecutive hypertensive patients (73 EH, 25 SH) with similar blood pressure levels completed two complementary measures of emotion processing: the 20-item Toronto Alexithymia Scale (TAS-20) and the Levels of Emotional Awareness Scale (LEAS). After controlling for confounding variables, LEAS score was lower in EH than SH (estimated means: 46.4 vs. 52.0; P = 0.028; effect size 0.52). TAS-20 scores did not differentiate EH from SH, but the differences were in the expected direction, with an effect size of 0.34 for TAS-20 total score. Neither psychometric measure was associated with the duration of hypertension or the presence of cardiovascular (CV) complications. These results are consistent with a contribution of an emotional or psychosomatic component in EH and may have practical implications for the nonpharmacological management of hypertension. They also demonstrate the utility of complementary measures of emotion processing in medically ill patients.

  16. Hypertension hos gravide

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Johansen, Marianne; Kamper, Anne Lise

    2009-01-01

    There are four major hypertensive disorders in pregnancy: chronic hypertension, gestational hypertension, preeclampsia and chronic hypertension with superimposed preeclampsia. The indications and efficacy of antihypertensive treatment of the different hypertensive disorders are assessed. Advantages...

  17. Types of Pulmonary Hypertension

    Science.gov (United States)

    ... Home / Hypertension Pulmonary Hypertension What Is Pulmonary hypertension (PULL-mun-ary HI- ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  18. Living with Pulmonary Hypertension

    Science.gov (United States)

    ... Home / Hypertension Pulmonary Hypertension What Is Pulmonary hypertension (PULL-mun-ary HI- ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  19. [Hypertension during pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, E.R.; Johansen, M.; Kamper, A.L.

    2009-01-01

    There are four major hypertensive disorders in pregnancy: chronic hypertension, gestational hypertension, preeclampsia and chronic hypertension with superimposed preeclampsia. The indications and efficacy of antihypertensive treatment of the different hypertensive disorders are assessed. Advantages...

  20. SH3 domain tyrosine phosphorylation--sites, role and evolution.

    Directory of Open Access Journals (Sweden)

    Zuzana Tatárová

    Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

  1. MeSH Now: automatic MeSH indexing at PubMed scale via learning to rank.

    Science.gov (United States)

    Mao, Yuqing; Lu, Zhiyong

    2017-04-17

    MeSH indexing is the task of assigning relevant MeSH terms based on a manual reading of scholarly publications by human indexers. The task is highly important for improving literature retrieval and many other scientific investigations in biomedical research. Unfortunately, given its manual nature, the process of MeSH indexing is both time-consuming (new articles are not immediately indexed until 2 or 3 months later) and costly (approximately ten dollars per article). In response, automatic indexing by computers has been previously proposed and attempted but remains challenging. In order to advance the state of the art in automatic MeSH indexing, a community-wide shared task called BioASQ was recently organized. We propose MeSH Now, an integrated approach that first uses multiple strategies to generate a combined list of candidate MeSH terms for a target article. Through a novel learning-to-rank framework, MeSH Now then ranks the list of candidate terms based on their relevance to the target article. Finally, MeSH Now selects the highest-ranked MeSH terms via a post-processing module. We assessed MeSH Now on two separate benchmarking datasets using traditional precision, recall and F 1 -score metrics. In both evaluations, MeSH Now consistently achieved over 0.60 in F-score, ranging from 0.610 to 0.612. Furthermore, additional experiments show that MeSH Now can be optimized by parallel computing in order to process MEDLINE documents on a large scale. We conclude that MeSH Now is a robust approach with state-of-the-art performance for automatic MeSH indexing and that MeSH Now is capable of processing PubMed scale documents within a reasonable time frame. http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/MeSHNow/ .

  2. Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein.

    Science.gov (United States)

    Garrity, P A; Rao, Y; Salecker, I; McGlade, J; Pawson, T; Zipursky, S L

    1996-05-31

    Mutations in the Drosophila gene dreadlocks (dock) disrupt photoreceptor cell (R cell) axon guidance and targeting. Genetic mosaic analysis and cell-type-specific expression of dock transgenes demonstrate dock is required in R cells for proper innervation. Dock protein contains one SH2 and three SH3 domains, implicating it in tyrosine kinase signaling, and is highly related to the human proto-oncogene Nck. Dock expression is detected in R cell growth cones in the target region. We propose Dock transmits signals in the growth cone in response to guidance and targeting cues. These findings provide an important step for dissection of signaling pathways regulating growth cone motility.

  3. Effect of levothyroxine therapy on hypertension in hypothyroid patients

    Directory of Open Access Journals (Sweden)

    A K Kapoor

    2012-01-01

    Full Text Available The aim of this study was to observe whether levothyroxine replacement therapy has an effect on hypertension in patients of hypothyroidism. This prospective study included all newly diagnosed cases of hypothyroidism (overt or subclinical with hypertension, of either sex between 21-70 years of age. Levothyroxine replacement therapy was administered continuously during study period. Patients were clinically assessed for blood pressure before and every 3-4 monthly on levothyroxine therapy. Statistical analysis was carried out using a paired Student’s t-test. During one year study period, out of 180 newly diagnosed hypothyroid cases enrolled, 88 had overt hypothyroidism (OH and 92 subclinical hypothyroidism (SH. Male: female ratio was 1: 6.5. Of these, hypertension was present in 51 (28.33% patients (33 OH and 18 SH. Only diastolic blood pressure was raised in 28(54.9% cases, systolic in 12 (23.53% and both systolic and diastolic in 11 (21.57% cases. Incidence of only diastolic hypertension was comparatively more in overt hypothyroidism (57.57% than subclinical hypothyroidism (50%. Complete reversal of hypertension was observed in 8 out of 17 SH and 18 out of 29 OH cases while partial reversal was noted in one case in each category. A statistically significant decrease in mean values of both systolic and diastolic blood pressure was observed in patients of SH as well as OH. Hypertension is fairly common in patients of hypothyroidism. Replacement therapy with levothyroxine is quite helpful in reversing hypertension, a potential cardiovascular risk factor.

  4. Pulmonary Hypertension

    Science.gov (United States)

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... that carry blood from your heart to your lungs become hard and narrow. Your heart has to ...

  5. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  6. Endokrin hypertension

    DEFF Research Database (Denmark)

    Poulsen, Per Løgstrup; Ibsen, Hans

    2009-01-01

    Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma-aldosterone-to-renin ......Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma...

  7. The role of SH3BP2 in the pathophysiology of cherubism

    Directory of Open Access Journals (Sweden)

    Reichenberger Ernst J

    2012-05-01

    Full Text Available Abstract Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans.

  8. Perioperative hypertension

    Directory of Open Access Journals (Sweden)

    G. Pinna

    2013-05-01

    Full Text Available BACKGROUND Perioperative hypertension is a situation whose management is suggested by the clinical judgement much more than clinical evidences. JNC 7 guidelines give a classification of blood pressure (BP, without any mention specifically dedicated to patients undergoing surgery. The ACC/AHA guidelines recommend deferring surgery if diastolic BP is above 110 mmHg and systolic BP is above 180 mmHg. AIM OF THE STUDY In this review we considered pathogenetic, clinical and therapeutic factors related to perioperative management of hypertensive patients. DISCUSSION In actual trend of the preoperative evaluation, alone hypertension is considered as a minor risk factor. BP values ≤ 180/110 mmHg do not influence the outcomes in patients who underwent noncardiac surgery. Therefore, in these conditions it’s not necessary to delay surgery. Hypertensive picks are possible during the operation, mostly because of the intubation, but, much more dangerous, falls of pressure are possible. The intraoperative arterial pressure should be maintained within 20% of the best estimated preoperative arterial pressure, especially in patients with markedly elevated preoperative pressures. After surgery the arterial BP can increase for stress factors, pain, hypoxia and hypercapnia, hypothermia and infusional liquids overload. For all these reasons a careful monitoring is mandatory. Anti-hypertensive medication should be continued during the postoperative period in patients with known and treated hypertension, as unplanned withdrawal of treatment can result in rebounded hypertension. The decision to give anti-hypertensive drugs must be made for each patient, taking into account their normal BP and their postoperative BP. With regard to the optimal treatment of the patient with poorly or uncontrolled hypertension in the perioperative evaluation, recent guidelines suggest that the best treatment may consider cardioselective β-blockers therapy, but also clonidin by

  9. MeSH ORA framework: R/Bioconductor packages to support MeSH over-representation analysis.

    Science.gov (United States)

    Tsuyuzaki, Koki; Morota, Gota; Ishii, Manabu; Nakazato, Takeru; Miyazaki, Satoru; Nikaido, Itoshi

    2015-02-15

    In genome-wide studies, over-representation analysis (ORA) against a set of genes is an essential step for biological interpretation. Many gene annotation resources and software platforms for ORA have been proposed. Recently, Medical Subject Headings (MeSH) terms, which are annotations of PubMed documents, have been used for ORA. MeSH enables the extraction of broader meaning from the gene lists and is expected to become an exhaustive annotation resource for ORA. However, the existing MeSH ORA software platforms are still not sufficient for several reasons. In this work, we developed an original MeSH ORA framework composed of six types of R packages, including MeSH.db, MeSH.AOR.db, MeSH.PCR.db, the org.MeSH.XXX.db-type packages, MeSHDbi, and meshr. Using our framework, users can easily conduct MeSH ORA. By utilizing the enriched MeSH terms, related PubMed documents can be retrieved and saved on local machines within this framework.

  10. Lessons from rat models of hypertension : from Goldblatt to genetic engineering

    NARCIS (Netherlands)

    Pinto, YM; Paul, M; Ganten, D

    Over the past 50 years various animal models of hypertension have been developed, predominantly in the rat. In this review we discuss the use of the rat as a model of hypertension, and evaluate what these models have taught us. Interestingly, the spontaneously hypertensive rat (SHR) is by far the

  11. Computed tomographic findings of spontaneous intracranial hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Seung Sook; Kim, Young Sook; Kim, Young Chul [College of Medicine, Chosun University, Kwangju (Korea, Republic of)

    1987-10-15

    Computed tomography (CT) was a reliable technique to evaluate the exact size and location of spontaneous intracranial hemorrhage and to predict it's prognosis. Fifty-nine cases of spontaneous intracranial hemorrhage were evaluated and reviewed by CT scan. The following results were obtained. 1. The sex ratio of male to female was 1 to 1.4, The highest incidence was in 6th and 7th decades. 2. The most common cause of spontaneous intracranial hemorrhage was hypertension (74.6%), followed by the aneurysm (13.5%), arteriovenous malformation (5.1%), occlusive vascular disease (3.4%), and blood dyscrasia (3.4%). 3. The most common location was basal ganglia and thalamic hemorrhage (37.3%), followed by lobar hemorrhage (27.1%), cerebellar hemorrhage (13.5%), and subarachnoid hemorrhage (11.9%). 4. Primary intraventricular hemorrhage carried the highest mortality. 5. The larger volume of hematoma, the higher the mortality rate.

  12. Renovascular hypertension

    International Nuclear Information System (INIS)

    Thomsen, H.S.; Sos, T.A.; Nielsen, S.L.; Koebenhavns Amts Sygehus, Herlev; Cornell Univ., New York

    1989-01-01

    Hypertension constitutes a major health problem and the challenge is to identify patients having 'surgically' curable renal vascular disease among the majority with so-called essential hypertension. The best of unsatisfactory diagnostic tests are renography and plasma renin activity both before and during angiotensin II blockade. The necessity of better screening tests has increased because of the recent advances in surgical techniques and especially percutaneous transluminal renal angioplasty. The latter has definitely become the method of choice for correction of suspected hemodynamically significant artery stenoses whenever technically feasible. With improved angioplasty techniques the risk of treating renal artery stenosis without hemodynamic and clinical importance (so-called cosmetic repair) has increased. Unfortunately randomized trials including surgery versus angioplasty are not available. It should be kept in mind that only after correction of the stenosis is achieved and the blood pressure has become normal, can the diagnosis of renovascular hypertension be made with certainty. (orig.)

  13. Evolution of the SH3 Domain Specificity Landscape in Yeasts.

    Directory of Open Access Journals (Sweden)

    Erik Verschueren

    Full Text Available To explore the conservation of Src homology 3 (SH3 domain-mediated networks in evolution, we compared the specificity landscape of these domains among four yeast species, Saccharomyces cerevisiae, Ashbya gossypii, Candida albicans, and Schizosaccharomyces pombe, encompassing 400 million years of evolution. We first aligned and catalogued the families of SH3-containing proteins in these four species to determine the relationships between homologous domains. Then, we tagged and purified all soluble SH3 domains (82 in total to perform a quantitative peptide assay (SPOT for each SH3 domain. All SPOT readouts were hierarchically clustered and we observed that the organization of the SH3 specificity landscape in three distinct profile classes remains conserved across these four yeast species. We also produced a specificity profile for each SH3 domain from manually aligned top SPOT hits and compared the within-family binding motif consensus. This analysis revealed a striking example of binding motif divergence in a C. albicans Rvs167 paralog, which cannot be explained by overall SH3 sequence or interface residue divergence, and we validated this specificity change with a yeast two-hybrid (Y2H assay. In addition, we show that position-weighted matrices (PWM compiled from SPOT assays can be used for binding motif screening in potential binding partners and present cases where motifs are either conserved or lost among homologous SH3 interacting proteins. Finally, by comparing pairwise SH3 sequence identity to binding profile correlation we show that for ~75% of all analyzed families the SH3 specificity profile was remarkably conserved over a large evolutionary distance. Thus, a high sequence identity within an SH3 domain family predicts conserved binding specificity, whereas divergence in sequence identity often coincided with a change in binding specificity within this family. As such, our results are important for future studies aimed at unraveling

  14. Modificação do padrão respiratório melhora o controle cardiovascular na hipertensão essencial Spontaneous respiratory modulation improves cardiovascular control in essential hypertension

    Directory of Open Access Journals (Sweden)

    Carlos Hermano da Justa Pinheiro

    2007-06-01

    Full Text Available FUNDAMENTO: Estudos recentes apontam os benefícios do controle da respiração na melhoria do barorreflexo, variabilidade da freqüência cardíaca e redução da pressão arterial em pacientes hipertensos. OBJETIVO: Avaliar os efeitos do treinamento com técnica de respiração lenta na modulação dos sistemas cardiovascular e respiratório de pacientes (n=10, homens e mulheres, com 45 a 60 anos de idade com hipertensão arterial essencial, assistidos em ambulatório. MÉTODOS: No delineamento do estudo, cada paciente foi utilizado como controle de si mesmo, sendo a coleta de dados realizada antes e após o período de intervenção. Foram avaliados parâmetros como variabilidade da freqüência cardíaca, pressão arterial sistólica, pressão arterial diastólica, pressão arterial média, ventilometria, cirtometria torácica e análise estatística dos dados. O treinamento respiratório utilizou exercícios de baixa freqüência e foi realizado duas vezes por semana durante um mês. Cada sessão teve duração de 30 minutos. RESULTADOS: Os resultados demonstraram redução da pressão arterial sistólica, da pressão arterial diastólica e da pressão arterial média (p BACKGROUND: Recent studies show that controlled breathing improves baroreflex and heart rate variability and lowers blood pressure in hypertensive patients. OBJECTIVE: To evaluate the effects of slow breathing training on cardiorespiratory system modulation of patients (n=10, men and women, ages ranging from 45 to 60 with essential hypertension seen in an outpatient setting. METHODS: According to the study design, each patient was used as his/her own control, and data were collected before and after the intervention. The following parameters were assessed: heart rate variability (HRV, systolic blood pressure (SBP, diastolic blood pressure (DBP, mean arterial blood pressure (MAP, respirometry, chest expansion measurement, and statistical data analysis. Respiratory training

  15. Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.

    Science.gov (United States)

    Rao, Donald D; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

    2016-08-01

    The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.

  16. Portal Hypertension

    Science.gov (United States)

    ... of Liver Disease .) Portal hypertension is abnormally high blood pressure in the portal vein (the large vein that brings blood from the ... imaging (MRI), or liver biopsy. Drugs can reduce blood pressure in the portal vein, but if bleeding in the digestive tract occurs, ...

  17. Expression and Production of SH2 Domain Proteins.

    Science.gov (United States)

    Liu, Bernard A; Ogiue-Ikeda, Mari; Machida, Kazuya

    2017-01-01

    The Src Homology 2 (SH2) domain lies at the heart of phosphotyrosine signaling, coordinating signaling events downstream of receptor tyrosine kinases (RTKs), adaptors, and scaffolds. Over a hundred SH2 domains are present in mammals, each having a unique specificity which determines its interactions with multiple binding partners. One of the essential tools necessary for studying and determining the role of SH2 domains in phosphotyrosine signaling is a set of soluble recombinant SH2 proteins. Here we describe methods, based on a broad experience with purification of all SH2 domains, for the production of SH2 domain proteins needed for proteomic and biochemical-based studies such as peptide arrays, mass-spectrometry, protein microarrays, reverse-phase microarrays, and high-throughput fluorescence polarization (HTP-FP). We describe stepwise protocols for expression and purification of SH2 domains using GST or poly His-tags, two widely adopted affinity tags. In addition, we address alternative approaches, challenges, and validation studies for assessing protein quality and provide general characteristics of purified human SH2 domains.

  18. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  19. Patterns of blood pressure variability in normotensive and hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; He, J; Wagner, A J

    1995-01-01

    We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR)...... the day; less pronounced in 2K,1C; and not detectable in SHR. There are regular patterns of blood pressure fluctuations and specific modifications to the patterns by different forms of hypertension.......We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR...

  20. [Progression of gestational hypertension to chronic hypertension].

    Science.gov (United States)

    Romero Gutiérrez, Gustavo; Muro Barragán, Sergio Alejandro; Ponce de León, Ana Lilia Ponce

    2009-09-01

    The gestational hypertension is the most frequent cause of hypertension during the pregnancy. The gestational hypertension is a provisional diagnosis only during the pregnancy; it is unknown the number of women with gestational hypertension who progress to chronic hypertension. To determine the number of women with gestational hypertension who progress to chronic hypertension. A cohort prospective study was carried out; we includedl96 patients with the diagnosis of gestational hypertension at the time of the interruption of the pregnancy; after 12 weeks, a follow up appointment was scheduled in order to measure the blood pressure and to determine how many patients progressed to chronic hypertension. The data were analyzed with arithmetic mean, standard error and percentage values. For the comparison of variables, the Chi2 test and a logistic regression analysis were used; an alpha value was set at 0.05. Thirteen patients (6.6%) with diagnosis of gestational hypertension progressed to chronic hypertension. It was found that advanced age (p = 0.007), high body mass index (p = 0.013) and the antecedent of hypertensive disease in a previous pregnancy (p = 0.048) were significantly associated with the progression to chronic hypertension. The overweight, advanced maternal age and the antecedent of hypertensive disorder in a previous pregnancy are the variables associated with the progression from gestational hypertension to chronic hypertension.

  1. Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

    Directory of Open Access Journals (Sweden)

    Fernanda S. Zamo

    2010-01-01

    Full Text Available BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1 hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate; 2 left ventricular hypertrophy; and 3 local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13 and adult (n=12. Hemodynamic signals (blood pressure, heart rate, blood pressure variability (BPV and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g, by myocyte diameter (μm and by relative fibrosis area (RFA, %. ACE and ACE2 activities were measured by fluorometry (UF/min, and plasma renin activity (PRA was assessed by a radioimmunoassay (ng/mL/h. Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU. RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent

  2. Hypertension Subtypes among Hypertensive Patients in Ibadan

    OpenAIRE

    Abiodun M. Adeoye; Adewole Adebiyi; Bamidele O. Tayo; Babatunde L. Salako; Adesola Ogunniyi; Richard S. Cooper

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% fema...

  3. Resistant hypertension.

    Science.gov (United States)

    Armario, P; Oliveras, A; de la Sierra, A

    2013-11-01

    A 53 year old woman with hypercholesterolemia treated with statins, with no history of cardiovascular disease, was referred to the Hypertension and Vascular Risk Unit for management of hypertension resistant to 4 antihypertensive agents at full doses. The patient had obesity, with a body mass index of 36.3kg/m(2) and office blood pressure 162/102mm Hg. Physical examination showed no data of interest. glucose 120mg/dl, glycated Hb: 6.4%, albuminuria 68mg/g, kidney function and study of the renin angiotensin system and other biochemical parameters were normal. Echocardiography: left ventricular mass, 131g/m(2) (normal, <110g/m(2)). True resistant hypertension was confirmed by ambulatory monitoring of blood pressure during 24h (153/89mm Hg). Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4.1mmol/l) following the treatment. After 8 weeks, blood pressure was well controlled: office blood pressure 132/86mm Hg and 24h-ambulatory blood pressure: 128/79mm Hg. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  4. Hypertension Subtypes among Hypertensive Patients in Ibadan

    Directory of Open Access Journals (Sweden)

    Abiodun M. Adeoye

    2014-01-01

    Full Text Available Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH, isolated systolic hypertension (ISH, isolated diastolic hypertension (IDH, and systolic-diastolic hypertension (SDH. Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5% and IDH (4.9% versus 4.7% were more prevalent among females, ISH (10.1% versus 6.2% was higher among males (P=0.048. Female subjects were more obese (P<0.0001 and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.

  5. Pulmonary Hypertension

    Science.gov (United States)

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

  6. [Combination treatment of hypertension in 2015].

    Science.gov (United States)

    Špinar, Jindřich; Vítovec, Jiří; Špinarová, Lenka; Bendová, Miroslava

    2015-05-01

    We present an overview of the present views on combination treatment and on fixed combinations in the treatment of hypertension according to guidelines of ESH/ESC and ČSH from 2013. The most frequently recommended dual combinations include a blocker of the renin-angiotensin system (ACEI or sartan) and a calcium channel blocker, and further a blocker of the renin-angiotensin system and a diuretic and a calcium channel blocker and a diuretic. In 2014 a fixed-dose combination of an ACE inhibitor (perindopril), a calcium channel blocker (amlodipine) and an diuretic (indapamide) appeared on the Czech market. Within the PIANIST study including 4 731 insufficiently controlled hypertensives, a fixed-dose triple combination of perindopril, amlodipine and indapamide led to a decrease in blood pressure by 28.3/13.8 mm Hg and to a sufficient control of hypertension in 92 % of patients. The advantage of fixed combinations primarily consists in greater compliance of patients and thereby in a better control of hypertension. About 1/3 of hypertensives need a triple combination for a satisfactory blood pressure control.

  7. Hypertension hos gravide

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Johansen, Marianne; Kamper, Anne Lise

    2009-01-01

    There are four major hypertensive disorders in pregnancy: chronic hypertension, gestational hypertension, preeclampsia and chronic hypertension with superimposed preeclampsia. The indications and efficacy of antihypertensive treatment of the different hypertensive disorders are assessed. Advantag...... and disadvantages of different classes of antihypertensive drugs during pregnancy and lactation are described....

  8. Organizational structures and communications on the SH 130 project.

    Science.gov (United States)

    2006-03-01

    This product summarizes the findings from research analyzing SH 130 organizational structures and communication flows. A set of guidelines pertaining to team organization and communication improvement and the design-build environment is also included...

  9. Fundamental modes of new dispersive SH-waves in ...

    Indian Academy of Sciences (India)

    Keywords. Piezoelectromagnetics; magnetoelectric effect; acoustic SH-waves in plates; wave dispersion; fundamental modes. ... Author Affiliations. A A Zakharenko1. International Institute of Zakharenko Waves (IIZWs), 660037, Krasnoyarsk-37, 17701, Krasnoyarsk, Russia ...

  10. Interproximal grooving in the Atapuerca-SH hominid dentitions.

    Science.gov (United States)

    Bermúdez de Castro, J M; Arsuaga, J L; Pérez, P J

    1997-03-01

    The dental sample recovered from the Sima de los Huesos (SH) Middle Pleistocene cave site of the Sierra de Atapuerca (Spain) includes 296 specimens. Interproximal wear grooves have been observed in 20 maxillary and mandibular posterior teeth belonging to at least five of the 32 individuals identified so far in the SH hypodigm. Interproximal grooving affected only the adults, and at an age between 25 and 40 years. The appearance, morphology, and location pattern of the SH wear grooves are similar to those reported in other fossil hominids and in more recent human populations. Two alternative proposals, the toothpicking and the fiber or sinew processing hypotheses, compete for explaining the formation of this anomalous wear. The characteristics observed in the wear grooves of the SH teeth are compatible only with the habitual probing of interdental spaces by means of hard and inflexible objects. Dietary grit may also have contributed to the abrasion of the root walls during the motion of the dental probes.

  11. Holographic Wavefront Correction for ShADOE LIDAR Receivers Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Current shared aperture diffractive optical elements (ShADOE) have intrinsic residual wavefront errors on the order of 50 waves which limits the angular resolution...

  12. Intracranial Hypertension Research Foundation

    Science.gov (United States)

    ... PARTNERSHIPS Meet our Fundraising Partners Tweet Welcome Intracranial hypertension (IH) is the general term for the neurological ... high. (Old names for IH include Benign Intracranial Hypertension and Pseudotumor Cerebri). The Intracranial Hypertension Research Foundation ...

  13. Hypertension and Spina Bifida

    Science.gov (United States)

    SBA National Resource Center: 800-621-3141 Hypertension A disease that often goes undetected. What is hypertension? Hypertension, also called high blood pressure , is a condition in which the arteries of ...

  14. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  15. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  16. White coat effect and masked uncontrolled hypertension in treated hypertensive-diabetic patients: Prevalence and target organ damage.

    Science.gov (United States)

    Leiria, Liana F; Severo, Mateus D; Ledur, Priscila S; Becker, Alexandre D; Aguiar, Fernanda M; Massierer, Daniela; Freitas, Valéria C; Schaan, Beatriz D; Gus, Miguel

    2015-09-01

    The association between hypertensive phenotypes of controlled hypertension (CH), white-coat effect (WCE), masked uncontrolled hypertension (MUH) and sustained hypertension (SH) with target organ damage have not been clearly established in diabetic hypertensive treated patients. The present study aims to evaluate the prevalence of the four phenotypes considering the current cut-off points for office and 24 h-ambulatory blood pressure monitoring (ABPM) and the association with left ventricle hypertrophy (LVH), diastolic function and nephropathy. Cross-sectional study with 304 patients on anti-hypertensive treatment aged 57.6 ± 6.1 years, who were submitted to ABPM and echocardiography. They were classified into CH (normal office BP and ABPM), WCE (high office BP and normal ABPM), MUH (normal office BP and high ABPM), and SH (high office BP and ABPM). Median HbA1c and diabetes duration were 7.9% (6.8-9.2), and 10 years (5-16), respectively. Prevalences of CH, WCE, MUH and SH were 27.3%, 17.1%, 18.8%, and 36.8%. MUH prevalence was higher than previously described. There was a significant increasing trend across the four groups in variables related to LVH (P ABPM beyond the traditional cardiovascular risk stratification tools has limitations, but is still useful in high-risk patients. Longitudinal studies could better evaluate the role of the use of ABPM in this scenario. Cut-off points for normality of office and ABPM influence the prevalences of WCH and MUH. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  17. Neonatal hypertension.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2017-03-01

    Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

  18. A unique set of SH3-SH3 interactions controls IB1 homodimerization

    DEFF Research Database (Denmark)

    Kristensen, Ole; Guenat, Sylvie; Dar, Imran

    2006-01-01

    Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components...... reduces IB1-dependent basal JNK activity in 293T cells. Impaired dimerization also results in a reduction in glucose transporter type 2 expression and in glucose-dependent insulin secretion in pancreatic beta-cells. Taken together, these results indicate that IB1 homodimerization through its SH3 domain...... has pleiotropic effects including regulation of the insulin secretion process....

  19. How Is Pulmonary Hypertension Treated?

    Science.gov (United States)

    ... Home / Hypertension Pulmonary Hypertension What Is Pulmonary hypertension (PULL-mun-ary HI- ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  20. Recurrent spontaneous attacks of dizziness.

    Science.gov (United States)

    Lempert, Thomas

    2012-10-01

    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  1. Assembling cyavanaprāsh, Ayurveda's best-selling medicine.

    Science.gov (United States)

    Bode, Maarten

    2015-04-01

    The paper discusses the many forms and representations of cyavanaprāsh, Ayurveda's best-selling medicine, already mentioned in Caraka's Compendium (c. 200 CE). The medicine's compositions, applications, and meanings, change over time and from locality to locality. Cyavanaprāsh is, for example, a patriotic formula, a booster of the immune system, a modern geriatric drug, and one of the elements in canonical Ayurvedic treatments. In the beginning of the 19th century cyavanaprāsh was a patriotic formula for fortifying Indian bodies and the nascent Indian nation. Nowadays the medicine is a Fast Moving Consumer Good (FMCG) and a money maker for Dabur India Ltd., the world largest Ayurvedic manufacturer. Instead of vitalising the nation its consumption now promises to make urban middle class consumers effectively modern. Branding and modern science must make Dabur Chyawanprash attractive in the eyes of these consumers. Ayurveda and cyavanaprāsh are also part of a global counter culture marked by neo-Orientalism and Ayurvedic medicines as facilitators of spirituality. The marketing of cyavanaprāsh by India's largest Ayurvedic manufacturer is used as a case study for discussing the proliferation of Ayurvedic brands and its critics. The imaging of Ayurvedic brands such as Dabur Chyawanprash threatens to obscure the fact that Ayurveda represents a unique way of looking upon health, disease and the human body. The proliferation of brands also makes Ayurvedic medicines more expensive and puts pressure on the natural environment as the main supplier of Ayurvedic ingredients.

  2. Hypertension in women

    OpenAIRE

    Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

    2013-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestationa...

  3. Modeling cometary photopolarimetric characteristics with Sh-matrix method

    Science.gov (United States)

    Kolokolova, L.; Petrov, D.

    2017-12-01

    Cometary dust is dominated by particles of complex shape and structure, which are often considered as fractal aggregates. Rigorous modeling of light scattering by such particles, even using parallelized codes and NASA supercomputer resources, is very computer time and memory consuming. We are presenting a new approach to modeling cometary dust that is based on the Sh-matrix technique (e.g., Petrov et al., JQSRT, 112, 2012). This method is based on the T-matrix technique (e.g., Mishchenko et al., JQSRT, 55, 1996) and was developed after it had been found that the shape-dependent factors could be separated from the size- and refractive-index-dependent factors and presented as a shape matrix, or Sh-matrix. Size and refractive index dependences are incorporated through analytical operations on the Sh-matrix to produce the elements of T-matrix. Sh-matrix method keeps all advantages of the T-matrix method, including analytical averaging over particle orientation. Moreover, the surface integrals describing the Sh-matrix elements themselves can be solvable analytically for particles of any shape. This makes Sh-matrix approach an effective technique to simulate light scattering by particles of complex shape and surface structure. In this paper, we present cometary dust as an ensemble of Gaussian random particles. The shape of these particles is described by a log-normal distribution of their radius length and direction (Muinonen, EMP, 72, 1996). Changing one of the parameters of this distribution, the correlation angle, from 0 to 90 deg., we can model a variety of particles from spheres to particles of a random complex shape. We survey the angular and spectral dependencies of intensity and polarization resulted from light scattering by such particles, studying how they depend on the particle shape, size, and composition (including porous particles to simulate aggregates) to find the best fit to the cometary observations.

  4. [Hypertensive crisis: urgency and hypertensive emergency].

    Science.gov (United States)

    Sobrino Martínez, Javier; Doménech Feria-Carot, Mónica; Morales Salinas, Alberto; Coca Payeras, Antonia

    2016-11-18

    Hypertensive crises lumped several clinical situations with different seriousness and prognosis. The differences between hypertensive urgency and hypertensive emergency depends on if this situation involves a vital risk for the patient. This risk is defined more by the severity of the organ damage than for the higher values of blood pressure. The hypertensive urgency not involves an immediately risk for the patient, for these reason, the treatment can be completed after discharged. Otherwise, the hypertensive emergency is a critical clinical condition that requires hospital assistance. Faced with a patient, with severe hypertension, asymptomatic or with unspecific symptoms we must be careful. First, we need to confirm the values of blood pressure, with several measures of blood pressure and investigate and treat factors, which triggered this situation. The objective of medical treatment for hypertensive urgency is to reduce blood pressure values (at least 20% of baseline values) but to avoid sudden reduction of these values. In hypertensive urgencies rapid acting drug should not be used because of the risk of ischemic stroke and use drugs with longer half-life. The cardiovascular risk of these patients is higher than that do not suffer hypertensive crisis. The treatment must be personalized in each hypertensive emergency and intravenous it’s the best route to treat these patients.

  5. Systolic hypertension in adult nigerians with hypertension

    International Nuclear Information System (INIS)

    Opadijo, O.G.; Salami, T.A.T.; Sanya, E.O.; Omotoso, A.B.O.

    2007-01-01

    To determine the prevalence of both systolic and diastolic hypertensions in relation to age and their impacts on target organ among adult Nigerians with hypertension. Newly diagnosed adult hypertensives, with blood pressure 140/90mm Hg, taken twice with mercury column sphygmomanometer at 3 weeks interval, were studied. The total number of hypertensive patients treated over this period was also taken into consideration. The newly diagnosed hypertensives were classified using JNC VI classification. The frequency of occurrence of target organ damage such as Left Ventricular Hypertrophy (LVH), heart failure, renal impairment etc. was charted according to systolic and or diastolic pressures. The occurrence of systolic or diastolic blood pressure was also related with the age of the patients. Blood metabolic parameters were compared in both systolic and diastolic blood pressures for their possible contributory role. Two thousand seven hundred and ninety-two adult hypertensive patients were managed over the study period. Of them, 218 (7.8%) were newly diagnosed and studied. There were 94 males and 124 females. Seventy-seven (35.3%) were aged 60 years and above with equal frequency in the gender. One hundred and seventy-eight (81.7%) cases had combined systolic and diastolic pressures. Twenty-nine (13.3%) patients had systolic hypertension. Twenty-five (86.2%) of these 29 were aged 50 years and above and 20 (69.0%) were aged 60 years and above. Eleven (5.0%) patients had isolated diastolic hypertension and they were all in the age bracket 40-49 years. Systolic blood pressure was found to be rising with advancing age while diastolic blood pressure peaked at mid 40's and declined. Target organ damage occurred more frequently with systolic hypertension and advancing age than with diastolic hypertension. Systolic hypertension occurred more frequently in this series of adult Nigerians with hypertension. It was higher with advancing age and associated with more target organ

  6. Entrainment of Spontaneously Hypertensive Rat Fibroblasts by Temperature Cycles

    Czech Academy of Sciences Publication Activity Database

    Sládek, Martin; Sumová, Alena

    2013-01-01

    Roč. 8, č. 10 (2013), e77010 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GPP305/10/P244; GA ČR(CZ) GAP303/11/0668 Institutional support: RVO:67985823 Keywords : circadian rhythms * temperature * entrainment * SHR * fibroblasts * phase response curve Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013

  7. Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats.

    Science.gov (United States)

    Perez, Christina M; Hazari, Mehdi S; Ledbetter, Allen D; Haykal-Coates, Najwa; Carll, Alex P; Cascio, Wayne E; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

    2015-01-01

    Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.).

  8. Reparação de defeitos ósseos em fêmures de ratos machos e fêmeas espontaneamente hipertensos: estudo histológico e histométrico Bone healing in drill hole defects in spontaneously hypertensive male and female rats' femurs: a histological and histometric study

    Directory of Open Access Journals (Sweden)

    Andresa Costa Pereira

    2007-01-01

    Full Text Available OBJETIVO: O objetivo deste estudo foi avaliar a reparação óssea em ratos espontaneamente hipertensos (SHR e compará-la com a de ratos normotensos, avaliando machos e fêmeas. MÉTODOS: Um defeito ósseo foi criado no fêmur esquerdo de 24 SHR (12 machos e 12 fêmeas e 24 ratos normotensos (12 machos e 12 fêmeas. Os animais foram divididos em dois grupos com diferentes períodos de sacrifício: sete e 21 dias após o procedimento cirúrgico. Após processamento laboratorial de rotina, as análises histológica e histométrica foram realizadas e os dados submetidos à análise de variância (ANOVA e ao teste de Tukey (5%. RESULTADOS: Machos e fêmeas do mesmo grupo apresentaram características histológicas similares. Após sete dias, todos os animais apresentaram trabéculas ósseas irregulares, entretanto, os osteoblastos periosteais eram achatados nos SHR, enquanto nos normotensos, essas células apresentavam formato cúbico. Após 21 dias, todos os espécimes mostraram fechamento linear em toda a extensão superficial do defeito ósseo e os SHR apresentaram osteoblastos achatados, enquanto os normotensos apresentaram células cúbicas circundando as trabéculas ósseas. A análise estatística dos dados histométricos indicou médias similares entre machos e fêmeas, exceto para ratos normotensos, aos sete dias. Além disso, aos 21 dias, foi observada maior neoformação óssea nos ratos hipertensos quando comparados aos normotensos, tanto machos quanto fêmeas. CONCLUSÃO: Concluiu-se que os animais SHR apresentaram maior neoformação e maturidade óssea nos defeitos que animais normotensos, no período de 21 dias após a cirurgia.OBJECTIVE: The aim of this study was to evaluate the bone healing in spontaneously hypertensive rats (SHR and compare the results with normotensive rats, evaluating male and female animals. METHODS: A bone drill defect was created in the left femur of 24 SHR (12 males and 12 females and 24 normotensive rats

  9. Fundamental modes of new dispersive SH-waves in ...

    Indian Academy of Sciences (India)

    sity functional theory, Ju and Guo [50] have investigated magnetic ordering dependence ... Theory and results. It is very important to know the suitable propagation directions of the shear horizontal. (SH) elastic waves when they can be coupled with both the electrical ..... [3] M Fiebig, V V Pavlov and R V Pisarev, J. Opt. Soc.

  10. Construction of lentiviral shRNA expression vector targeting ...

    African Journals Online (AJOL)

    DNA oligo was cloned into lentiviral expression vector, and then polymerase chain reaction (PCR) and sequencing analyses were conducted to verify the constructs. The verified vectors were co-transfected into 293FT cells that could produce lentiviral. shRNA lentiviruses from the selected constructs were propagated and ...

  11. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  12. Portal hypertension.

    Science.gov (United States)

    Collini, F J; Brener, B

    1990-02-01

    The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective

  13. Palaeodemography of the Atapuerca-SH Middle Pleistocene hominid sample.

    Science.gov (United States)

    Bermúdez de Castro, J M; Nicolás, M E

    1997-01-01

    We report here on the palaeodemographic analysis of the hominid sample recovered to date from the Sima de los Huesos (SH) Middle Pleistocene cave site in the Sierra de Atapuerca (Burgos, Spain). The analysis of the mandibular, maxillary, and dental remains has made it possible to estimate that a minimum of 32 individuals, who probably belonged to the same biological population, are represented in the current SH human hypodigm. The remains of nine-individuals are assigned to males, and nine to females, suggesting that a 1:1 sex ratio characterizes this hominid sample. The survivorship curve shows a low representation of infants and children, a high mortality among the adolescents and prime-age adults, and a low older adult mortality. Longevity was probably no greater than 40 years. This mortality pattern (adolescents and adults); which in some aspects resembles that observed in Neandertals, is quite different from those reported for recent foraging human groups. The adult age-at-death distribution of the SH hominid sample appears to be neither the consequence of underaging the older adults, nor of differential preservation or of the recognition of skeletal remains. Thus if we accept that they had a life history pattern similar to that of modern humans there would appear to be a clear contradiction between the demographic distribution and the demographic viability of the population represented by the SH hominid fossils. The possible representational bias of the SH hominid sample, as well as some aspects of the reproductive biology of the Pleistocene populations are also discussed.

  14. [Hypertension in the elderly].

    Science.gov (United States)

    Handschin, Anja; Henny-Fullin, Katja; Buess, Daniel; Leuppi, Jörg; Dieterle, Thomas

    2015-06-01

    Arterial hypertension remains the most important risk factor for cardiovascular and renal diseases. In view of an increasing prevalence with older age and an increasingly aging population, the treatment of elderly patients with arterial hypertension will become increasingly important in daily practice. Arterial hypertension in the elderly differs in many aspects from arterial hypertension in younger patients. For example, isolated systolic hypertension is the predominant form of arterial hypertension in the elderly. In comparison to younger patients, treatment of hypertension in the elderly is less well investigated. However, available data suggest that lowering of blood pressure in the elderly and very elderly reduces the risk of heart failure, stroke, and even mortality. The best evidence for the treatment of hypertension in the elderly exists for diuretics and calcium antagonists. However, the primary choice of antihypertensive therapy should be guided by the presence of existing cardiovascular and/or renal comorbidities.

  15. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  16. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  17. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  18. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  19. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  20. Prevalence of hypertension and other cardiovascular risk factors in subjects with subclinical hypothyroidism.

    Science.gov (United States)

    Gonzalez Gil, Lidia; de la Sierra, Alejandro

    2017-04-21

    To assess the prevalence of hypertension, diabetes, and dyslipidaemia in subjects with subclinical hypothyroidism (SH) in comparison with an age- and sex-matched control group. Case-control study with 240 subjects with SH and 480 controls carried out on patients aged 35-75 years admitted to a Primary Care Centre. The prevalence of hypertension, diabetes and dyslipidaemia, as well as blood pressure, plasma glucose, and lipid profilses, were evaluated in both groups. No differences were observed neither in the prevalence of hypertension (34.2% vs. 29.6%) or diabetes (12.1% vs. 10%) nor in mean values of blood pressure or plasma fasting glucose. Subjects with SH had an increased prevalence of lipid abnormalities (72.1% vs. 57.7%; P<.001), and increased mean values of total cholesterol (205±34 vs. 193±35mg/dL; P<.001), compared to the control group. Patients with SH have an increased prevalence of lipid abnormalities. This can be responsible for an increased cardiovascular risk in such patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  1. Genetik og hypertension

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tarnow, Lisa; Pedersen, Erling Bjerregaard

    2009-01-01

    Monogenic forms of hypertension are very rare, but have a well-characterized heredity. Primary hypertension is very common with a complex and polygenic heredity. Primary hypertension arises due to an interaction between multiple genetic and environmental factors. Its heredity is unknown, although...

  2. Hypertension and sexual dysfunction

    African Journals Online (AJOL)

    Review Article: Hypertension and sexual dysfunction. 117. Vol 54 No 2. S Afr Fam Pract 2012. Introduction. Hypertension is a major independent cardiovascular risk factor, and also a marker of survival risk. Quality of life during the treatment of hypertension is an important health issue, as one in every five treated patients ...

  3. Idiopathic portal hypertension

    International Nuclear Information System (INIS)

    Han, Tae Kyun; Ryu, Dae Sik; Kim, Heung Chul; Hur, Hun; Eom, Kyeung Tae; Namkung, Sook; Park, Man Soo; Hwang, Woo Chul; Lee, Kwan Seop

    1996-01-01

    To describe the radiologic findings of idiopathic portal hypertension and to find the points of differentiation between idiopathic portal hypertension and liver cirrhosis. Four portograms in five patients who for four years had suffered from pathologically confirmed idiopathic portal hypertension were retrospectively analyzed and compared with a portogram obtained from a control subject with liver cirrhosis. Portographic finding s of idiopathic portal hypertension were paucity of medium-sized portal branches, irregular and obtuse-angled division of peripheral branches, abrupt interruption and an avascular area beneath the liver margin. A portogram of idiopathic portal hypertension may be useful in differentiation this and liver cirrhosis

  4. SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

    Directory of Open Access Journals (Sweden)

    M. Yu. Yukina

    2016-01-01

    Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

  5. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  6. Effects on atrial fibrillation in aged hypertensive rats by Ca(2+)-activated K(+) channel inhibition

    DEFF Research Database (Denmark)

    Diness, Jonas Goldin; Skibsbye, Lasse; Jespersen, Thomas

    2011-01-01

    hypertensive rats were more vulnerable to AF induction both by S2 stimulation and burst pacing. Vehicle affected neither the atrial effective refractory period nor AF duration. SK channel inhibition with NS8593 and UCL1684 significantly increased the atrial effective refractory period and decreased AF duration......We have shown previously that inhibition of small conductance Ca(2+)-activated K(+) (SK) channels is antiarrhythmic in models of acutely induced atrial fibrillation (AF). These models, however, do not take into account that AF derives from a wide range of predisposing factors, the most prevalent...... being hypertension. In this study we assessed the effects of two different SK channel inhibitors, NS8593 and UCL1684, in aging, spontaneously hypertensive rats to examine their antiarrhythmic properties in a setting of hypertension-induced atrial remodeling. Male spontaneously hypertensive rats...

  7. Anti-Renal Fibrotic Effect of Exercise Training in Hypertension

    Directory of Open Access Journals (Sweden)

    Chiu-Ching Huang

    2018-02-01

    Full Text Available The purpose of this study was to evaluate the effects of exercise training on renal fibrosis in hypertensive rats. Masson’s trichrome staining and Western blotting were performed on the excised renal cortex from sixteen male spontaneously hypertensive rats (SHR, which were randomly divided into either a sedentary hypertensive group (SHR or exercise hypertensive group (SHR-EX, running on an exercise treadmill for 60 min/day, 5 sessions/week, for 12 weeks, and from eight male Wistar-Kyoto rats which served as a sedentary normotensive group (WKY. The systolic blood pressure (SBP and renal fibrosis in hypertensive rats improved after exercise training. The inflammatory-related protein levels of interleukin-6 (IL-6 and cyclooxygenase-2 (COX-2, as well as the fibrotic-related protein levels of transforming growth factor-beta (TGF-β, phospho-Smad2/3 (p-Smad2/3, connective tissue growth factor (CTGF, matrix metalloproteinase-9 (MMP-9, and matrix metalloproteinase-2 (MMP-2 were decreased in the SHR-EX group when compared with the SHR group. Exercise training suppressed the hypertension-induced renal cortical inflammatory and fibrotic pathways in hypertensive rat models. These findings might indicate a new therapeutic effect for exercise training to prevent renal fibrosis in hypertensive nephropathy.

  8. Bariatric Surgery and Hypertension.

    Science.gov (United States)

    Owen, Jonathan G; Yazdi, Farshid; Reisin, Efrain

    2017-12-08

    Obesity continues to increase in prevalence worldwide. Hypertension has long been associated with obesity, and weight loss continues to be a first-line therapy in the treatment of hypertension. Lifestyle modification and pharmacologic therapy, however, often meet with treatment failure. Bariatric surgery continues to be the most successful approach to sustained weight loss. This review focuses on the underlying physiologic mechanisms of obesity-hypertension, and the impact of bariatric surgery on the treatment of hypertension. Current available literature on the physiologic mechanisms of obesity-hypertension, and the major trials, meta-analyses and systematic reviews of the impact of bariatric surgery procedures on hypertension are reviewed. Evidence suggests significant improvement in obesity-hypertension in patients who undergo surgical weight-reduction procedures. Malabsorptive techniques such as the Roux-en-Y gastric bypass or surgical resection techniques such as laparoscopic sleeve gastrectomy appear to offer superior results in regards to hypertension control over restrictive techniques such as Gastric Banding. Though long-term control of hypertension following surgery remains a concern, available follow-up post-operative data of up to 10 years suggests a sustained, if lessened, effect on hypertension control over time. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Detection and characterization of partially unfolded oligomers of the SH3 domain of α-Spectrin

    NARCIS (Netherlands)

    Casares, S.; Sadqi, M.; López-Mayorga, O.; Conejero-Lara, F.; van Nuland, N.A.J.

    2004-01-01

    For the purpose of equilibrium and kinetic folding-unfolding studies, the SH3 domain of α-spectrin (spc-SH3) has long been considered a classic two-state folding protein. In this work we have indeed observed that the thermal unfolding curves of spc-SH3 measured at pH 3.0 by differential scanning

  10. Feature engineering for MEDLINE citation categorization with MeSH.

    Science.gov (United States)

    Jimeno Yepes, Antonio Jose; Plaza, Laura; Carrillo-de-Albornoz, Jorge; Mork, James G; Aronson, Alan R

    2015-04-08

    Research in biomedical text categorization has mostly used the bag-of-words representation. Other more sophisticated representations of text based on syntactic, semantic and argumentative properties have been less studied. In this paper, we evaluate the impact of different text representations of biomedical texts as features for reproducing the MeSH annotations of some of the most frequent MeSH headings. In addition to unigrams and bigrams, these features include noun phrases, citation meta-data, citation structure, and semantic annotation of the citations. Traditional features like unigrams and bigrams exhibit strong performance compared to other feature sets. Little or no improvement is obtained when using meta-data or citation structure. Noun phrases are too sparse and thus have lower performance compared to more traditional features. Conceptual annotation of the texts by MetaMap shows similar performance compared to unigrams, but adding concepts from the UMLS taxonomy does not improve the performance of using only mapped concepts. The combination of all the features performs largely better than any individual feature set considered. In addition, this combination improves the performance of a state-of-the-art MeSH indexer. Concerning the machine learning algorithms, we find that those that are more resilient to class imbalance largely obtain better performance. We conclude that even though traditional features such as unigrams and bigrams have strong performance compared to other features, it is possible to combine them to effectively improve the performance of the bag-of-words representation. We have also found that the combination of the learning algorithm and feature sets has an influence in the overall performance of the system. Moreover, using learning algorithms resilient to class imbalance largely improves performance. However, when using a large set of features, consideration needs to be taken with algorithms due to the risk of over-fitting. Specific

  11. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  12. Coloring Jupiter's clouds: Radiolysis of ammonium hydrosulfide (NH4SH)

    Science.gov (United States)

    Loeffler, Mark J.; Hudson, Reggie L.

    2018-03-01

    Here we present our recent studies on the color and spectral reflectance changes induced by ∼0.9 MeV proton irradiation of ammonium hydrosulfide, NH4SH, a compound predicted to be an important tropospheric cloud component of Jupiter and other giant planets. Ultraviolet-visible spectroscopy was used to observe and identify reaction products in the ice sample and digital photography was used to document the corresponding color changes at 10-160 K. Our experiments clearly show that the resulting color of the sample depends not only on the irradiation dose but also the irradiation temperature. Furthermore, unlike in our most recent studies of irradiation of NH4SH at 120 K, which showed that higher irradiation doses caused the sample to appear green, the lower temperature studies now show that the sample becomes red after irradiation. However, comparison of these lower temperature spectra over the entire spectral range observed by HST shows that even though the color and spectrum resemble the color and spectrum of the GRS, there is still enough difference to suggest that another component may be needed to adequately fit spectra of the GRS and other red regions of Jupiter's clouds. Regardless, the presence of NH4SH in the atmosphere of Jupiter and other gas giants, combined with this compound's clear alteration via radiolysis, suggests that its contribution to the ultraviolet-visible spectra of any of these object's clouds is significant.

  13. Role of SH3b binding domain in a natural deletion mutant of Kayvirus endolysin LysF1 with a broad range of lytic activity.

    Science.gov (United States)

    Benešík, Martin; Nováček, Jiří; Janda, Lubomír; Dopitová, Radka; Pernisová, Markéta; Melková, Kateřina; Tišáková, Lenka; Doškař, Jiří; Žídek, Lukáš; Hejátko, Jan; Pantůček, Roman

    2018-02-01

    The spontaneous host-range mutants 812F1 and K1/420 are derived from polyvalent phage 812 that is almost identical to phage K, belonging to family Myoviridae and genus Kayvirus. Phage K1/420 is used for the phage therapy of staphylococcal infections. Endolysin of these mutants designated LysF1, consisting of an N-terminal cysteine-histidine-dependent aminohydrolase/peptidase (CHAP) domain and C-terminal SH3b cell wall-binding domain, has deleted middle amidase domain compared to wild-type endolysin. In this work, LysF1 and both its domains were prepared as recombinant proteins and their function was analyzed. LysF1 had an antimicrobial effect on 31 Staphylococcus species of the 43 tested. SH3b domain influenced antimicrobial activity of LysF1, since the lytic activity of the truncated variant containing the CHAP domain alone was decreased. The results of a co-sedimentation assay of SH3b domain showed that it was able to bind to three types of purified staphylococcal peptidoglycan 11.2, 11.3, and 11.8 that differ in their peptide bridge, but also to the peptidoglycan type 11.5 of Streptococcus uberis, and this capability was verified in vivo using the fusion protein with GFP and fluorescence microscopy. Using several different approaches, including NMR, we have not confirmed the previously proposed interaction of the SH3b domain with the pentaglycine bridge in the bacterial cell wall. The new naturally raised deletion mutant endolysin LysF1 is smaller than LysK, has a broad lytic spectrum, and therefore is an appropriate enzyme for practical use. The binding spectrum of SH3b domain covering all known staphylococcal peptidoglycan types is a promising feature for creating new chimeolysins by combining it with more effective catalytic domains.

  14. Risk factors for recurrent spontaneous epistaxis.

    Science.gov (United States)

    Abrich, Victor; Brozek, Annabelle; Boyle, Timothy R; Chyou, Po-Huang; Yale, Steven H

    2014-12-01

    To identify risk factors associated with spontaneous recurrent epistaxis. This was a retrospective cohort study assessing patients in the Marshfield Clinic system diagnosed as having epistaxis between January 1, 1991, and January 1, 2011. There were 461 cases with at least 2 episodes of spontaneous epistaxis within 3 years and 912 controls with only 1 episode in the same time frame. More than 50 potential risk factors were investigated, including demographic features, substance use, nasal anatomical abnormalities, nasal infectious and inflammatory processes, medical comorbidities, medications, and laboratory values. A Cox proportional hazards regression modeling approach was used to calculate hazard ratios of epistaxis recurrence. Traditional risk factors for epistaxis, including nasal perforation, nasal septum deviation, rhinitis, sinusitis, and upper respiratory tract infection, did not increase the risk of recurrence. Significant risk factors for recurrent epistaxis included congestive heart failure, diabetes mellitus, hypertension, and a history of anemia. Warfarin use increased the risk of recurrence, independent of international normalized ratio. Aspirin and clopidogrel were not found to increase the risk of recurrence. Few major adverse cardiovascular events were observed within 30 days of the first epistaxis event. Congestive heart failure is an underappreciated risk factor for recurrent epistaxis. Hypertension and diabetes mellitus may induce atherosclerotic changes in the nasal vessels, making them friable and more at risk for bleeding. Patients with recurrent epistaxis may also be more susceptible to developing anemia. Physicians should promote antiplatelet and antithrombotic medication adherence despite an increased propensity for recurrent epistaxis to prevent major adverse cardiovascular events. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. Induction of Apoptosis by Hypertension Via Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Yingying Sun

    2015-02-01

    Full Text Available Background/Aims: Endoplasmic reticulum (ER stress is one of the intrinsic apoptosis pathways, and cardiac apoptosis can occur in cardiovascular diseases, such as hypertension. However, the mechanisms by which ER stress leads to apoptosis remain enigmatic, particularly in the progression from cardiac hypertrophy to diastolic heart failure due to hypertension. Methods: We used spontaneously hypertensive rats (SHRs to investigate possible signalling pathways for ER stress. Results: We found that cardiac protein and mRNA levels of glucose-regulated protein 78 were up-regulated. In addition, the CHOP- and caspase-12-dependent pathways, but not that of JNK, were activated in the SHR rats. Conclusions: These results suggest that ER stress can contribute to myocardial apoptosis during hypertensive disease.

  16. Effects of antidepressants on DSP4/CPT-induced DNA damage response in neuroblastoma SH-SY5Y cells

    Science.gov (United States)

    Wang, Yan; Hilton, Benjamin A.; Cui, Kui; Zhu, Meng-Yang

    2015-01-01

    DNA damage is a form of cell stress and injury. Increased systemic DNA damage is related to the pathogenic development of neurodegenerative diseases. Depression occurs in a relatively high percentage of patients suffering from degenerative diseases, for whom antidepressants are often used to relieve depressive symptoms. However, few studies have attempted to elucidate why different groups of antidepressants have similar effects on relieving symptoms of depression. Previously, we demonstrated that neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)- and camptothecin (CPT)-induced the DNA damage response in SH-SY5Y cells, and DSP4 caused cell cycle arrest which was predominately in the S-phase. The present study shows that CPT treatment also resulted in similar cell cycle arrest. Some classic antidepressants could reduce the DNA damage response induced by DSP4 or CPT in SH-SY5Y cells. Cell viability examination demonstrated that both DSP4 and CPT caused cell death, which was prevented by spontaneous administration of some tested antidepressants. Flow cytometric analysis demonstrated that a majority of the tested antidepressants protect cells from being arrested in S-phase. These results suggest that blocking the DNA damage response may be an important pharmacologic characteristic of antidepressants. Exploring the underlying mechanisms may allow for advances in the effort to improve therapeutic strategies for depression appearing in degenerative and psychiatric diseases. PMID:26038195

  17. Clinical features of multiple spontaneous intracerebral hemorrhages

    Directory of Open Access Journals (Sweden)

    Tao CHANG

    2016-01-01

    Full Text Available Objective To analyze the clinical features of multiple spontaneous intracerebral hemorrhages (MICH. Methods Conservative therapy, puncture and drainage, hematoma removal and/or decompressive craniectomy were used in the treatment of 630 intracerebral hemorrhage (ICH patients, who were divided into 2 groups: 30 cases with MICH and another 600 cases with solitary intracerebral hemorrhage (SICH. Three months after onset, modified Rankin Scale (mRS was used to evaluate the prognosis of all cases. Results Compared with patients in SICH group, the occurrence rate of hypertension > 5 years (P = 0.008, diabetes mellitus (P = 0.024, hypercholesterolemia (P = 0.050 and previous ischemic stroke (P = 0.026 were all significantly higher in MICH group. The mean arterial pressure (MAP level (P = 0.002 and the incidence of limb movement disorder (P = 0.000 were significantly higher in patients with MICH than those with SICH. Basal ganglia and thalamus were the predilection sites of hematoma (P = 0.001. Patients with MICH had worse prognosis compared to those with SICH 3 months after onset (P = 0.006. Conclusions Hypertension > 5 years, diabetes mellitus, hypercholesterolemia and ischemic stroke were identified to be the pathophysiological basis of MICH in this study. All patients with MICH had more serious clinical manifestations after onset and worse prognosis. DOI: 10.3969/j.issn.1672-6731.2016.01.008

  18. Hypertension in Metabolic Syndrome: Vascular Pathophysiology

    Science.gov (United States)

    Mendizábal, Yolanda; Llorens, Silvia; Nava, Eduardo

    2013-01-01

    Metabolic syndrome is a cluster of metabolic and cardiovascular symptoms: insulin resistance (IR), obesity, dyslipemia. Hypertension and vascular disorders are central to this syndrome. After a brief historical review, we discuss the role of sympathetic tone. Subsequently, we examine the link between endothelial dysfunction and IR. NO is involved in the insulin-elicited capillary vasodilatation. The insulin-signaling pathways causing NO release are different to the classical. There is a vasodilatory pathway with activation of NO synthase through Akt, and a vasoconstrictor pathway that involves the release of endothelin-1 via MAPK. IR is associated with an imbalance between both pathways in favour of the vasoconstrictor one. We also consider the link between hypertension and IR: the insulin hypothesis of hypertension. Next we discuss the importance of perivascular adipose tissue and the role of adipokines that possess vasoactive properties. Finally, animal models used in the study of vascular function of metabolic syndrome are reviewed. In particular, the Zucker fatty rat and the spontaneously hypertensive obese rat (SHROB). This one suffers macro- and microvascular malfunction due to a failure in the NO system and an abnormally high release of vasoconstrictor prostaglandins, all this alleviated with glitazones used for metabolic syndrome therapy. PMID:23573411

  19. Hypertension in Metabolic Syndrome: Vascular Pathophysiology

    Directory of Open Access Journals (Sweden)

    Yolanda Mendizábal

    2013-01-01

    Full Text Available Metabolic syndrome is a cluster of metabolic and cardiovascular symptoms: insulin resistance (IR, obesity, dyslipemia. Hypertension and vascular disorders are central to this syndrome. After a brief historical review, we discuss the role of sympathetic tone. Subsequently, we examine the link between endothelial dysfunction and IR. NO is involved in the insulin-elicited capillary vasodilatation. The insulin-signaling pathways causing NO release are different to the classical. There is a vasodilatory pathway with activation of NO synthase through Akt, and a vasoconstrictor pathway that involves the release of endothelin-1 via MAPK. IR is associated with an imbalance between both pathways in favour of the vasoconstrictor one. We also consider the link between hypertension and IR: the insulin hypothesis of hypertension. Next we discuss the importance of perivascular adipose tissue and the role of adipokines that possess vasoactive properties. Finally, animal models used in the study of vascular function of metabolic syndrome are reviewed. In particular, the Zucker fatty rat and the spontaneously hypertensive obese rat (SHROB. This one suffers macro- and microvascular malfunction due to a failure in the NO system and an abnormally high release of vasoconstrictor prostaglandins, all this alleviated with glitazones used for metabolic syndrome therapy.

  20. Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand.

    Science.gov (United States)

    Plummer, M S; Holland, D R; Shahripour, A; Lunney, E A; Fergus, J H; Marks, J S; McConnell, P; Mueller, W T; Sawyer, T K

    1997-11-07

    The specific association of an SH2 domain with a phosphotyrosine (pTyr)-containing sequence of another protein precipitates a cascade of intracellular molecular interactions (signals) which effect a wide range of intracellular processes. The nonreceptor tyrosine kinase Src, which has been associated with breast cancer and osteoporosis, contains an SH2 domain. Inhibition of Src SH2-phosphoprotein interactions by small molecules will aid biological proof-of-concept studies which may lead to the development of novel therapeutic agents. Structure-based design efforts have focused on reducing the size and charge of Src SH2 ligands while increasing their ability to penetrate cells and reach the intracellular Src SH2 domain target. In this report we describe the synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.

  1. Hypertensive crisis in children.

    Science.gov (United States)

    Chandar, Jayanthi; Zilleruelo, Gastón

    2012-05-01

    Hypertensive crisis is rare in children and is usually secondary to an underlying disease. There is strong evidence that the renin-angiotensin system plays an important role in the genesis of hypertensive crisis. An important principle in the management of children with hypertensive crisis is to determine if severe hypertension is chronic, acute, or acute-on-chronic. When it is associated with signs of end-organ damage such as encephalopathy, congestive cardiac failure or renal failure, there is an emergent need to lower blood pressures to 25-30% of the original value and then accomplish a gradual reduction in blood pressure. Precipitous drops in blood pressure can result in impairment of perfusion of vital organs. Medications commonly used to treat hypertensive crisis in children are nicardipine, labetalol and sodium nitroprusside. In this review, we discuss the pathophysiology, differential diagnosis and recent developments in management of hypertensive crisis in children.

  2. Hypertension in Danish seafarers

    DEFF Research Database (Denmark)

    Tu, Mingshan; Jepsen, Jørgen Riis

    2016-01-01

    Background: Due to the high prevalence of arterial hypertension and its role in the development of athe- rosclerosis, myocardial infarction and stroke, hypertension is a major public health challenge worldwide. There is limited knowledge of the prevalence of hypertension among seafarers who......, however, are known to have an excess morbidity and mortality from these disorders. This article addresses the prevalence of hypertension among Danish seafarers and discusses potential risk factors for hypertension in maritime settings. Materials and methods: A representative sample of 629 Danish seafarers...... who had statutory medical examinations was studied from the beginning of October 2011 to the end of June 2012. The medical examination included measurements of blood pressure. The prevalence of hypertension in the study po- pulation was stratified by age, work place on board, smoking status, alcohol...

  3. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  4. Hypertension og hyperlipidaemi

    DEFF Research Database (Denmark)

    Hansen, Henrik Steen; Larsen, Mogens Lytken

    2009-01-01

    Hypertension and hyperlipidemia are well-established and partially overlapping risk factors for cardiovascular disease. Analyses of cardiovascular morbidity in relationship to changes in blood pressure and in serum cholesterol levels have shown that combined reduction of both risk factors...... are important to achieve a reduction in morbidity. Statins have been shown to be effective in preventing both coronary and cerebrovascular events in both hypertensive and normotensive cases. Consequently, most recent guidelines recommend that statin treatment be considered in hypertensive patients aged less...

  5. [Hypertension in women].

    Science.gov (United States)

    Tagle, Rodrigo; Tagle V, Rodrigo; Acevedo, Mónica; Valdés, Gloria

    2013-02-01

    The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.

  6. The new hypertension guidelines.

    Science.gov (United States)

    Stern, Ralph H

    2013-10-01

    The Canadian Hypertension Education Program (CHEP) has published guidelines annually since 2000. The CHEP guidelines are a model of concise, comprehensive, up-to-date, evidence-rated guidelines for physicians who diagnose and treat hypertension. The guidelines address measurement of blood pressure and the definition of hypertension, secondary hypertension evaluation and treatment, and blood pressure targets and medication choices in patients with and without compelling indications. This review describes CHEP's process for developing guidelines and provides an overview of the 2013 recommendations. ©2013 Wiley Periodicals, Inc.

  7. 42. Hypertension: Morbidity review

    Directory of Open Access Journals (Sweden)

    Hamzullah khan

    2015-10-01

    Conclusions: hypertension is a major modifiable risk factor for coronary artery disease, stroke, eye abnormalities and end stage renal disease, which require proper counseling and management of patients.

  8. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  9. Star formation around the HII region Sh2-235

    OpenAIRE

    Kirsanova, M. S.; Sobolev, A. M.; Thomasson, M.; Wiebe, D. S.; Johansson, L. E. B.; Seleznev, A. F.

    2008-01-01

    We present a picture of star formation around the HII region Sh2-235 (S235) based upon data on the spatial distribution of young stellar clusters and the distribution and kinematics of molecular gas around S235. We observed 13CO(1-0) and CS(2-1) emission toward S235 with the Onsala Space Observatory 20-m telescope and analysed the star