Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats

2005 ◽  
Vol 108 (4) ◽  
pp. 349-355 ◽  
Author(s):  
Daniele G. BEZERRA ◽  
Carlos A. MANDARIM-de-LACERDA
Keyword(s):  
Left Ventricle ◽  
Spontaneously Hypertensive Rats ◽  
Renal Cortex ◽  
Interstitial Fibrosis ◽  
Treated Group ◽  
Left Ventricular ◽  
Control Group ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Significant Difference

The aim of the present study was to investigate the possibility of different effects of the hydrophobic statin simvastatin and the hydrophilic statin pravastatin on the remodelling process in the overloaded left ventricle and renal cortex of SHRs (spontaneously hypertensive rats). Fifteen SHRs were treated for 40 days with simvastatin, pravastatin or placebo (water) via orogastric administration. Left ventricle and renal cortex were examined by light microscopy and stereology. LV (left ventricular) cardiomyocyte nuclei (N[cmn]) and glomeruli (N[gl]) numbers were estimated by the dissector method. BP (blood pressure) and serum triacylglycerols (triglycerides) were lower in the statin-treated groups than in the untreated control group. The volume density of the interstitial connective tissue was smaller and length density of the intramyocardial arteries, as well as the arteries/cardiomyocyte ratio, was greater in the statin-treated groups than in the control group. No difference was observed between the two statin-treated groups. The cross-sectional cardiomyocyte area was significantly smaller in the simvastatin-treated group than in the control or pravastatin-treated groups, and it was smaller in the pravastatin-treated group than in the control group. N[cmn] and N[gl] were greater in the two statin-treated groups than in the control group, but no significant difference was observed between the two statin-treated groups. In conclusion, administration of the statins simvastatin and pravastatin to SHRs effectively prevented the elevation in BP and serum triaclyglycerols, and also attenuated adverse cardiac and kidney remodelling by preventing LV hypertrophy, enhancing myocardial vascularization with the decrease in interstitial fibrosis and attenuating cardiomyocyte and glomerular loss.

Abstract 408: Thioredoxin-1 Gene Delivery Induces Hemeoxygenase-1 Mediated Myocardial Preservation after Chronic Infarction in Spontaneously Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
SureshVarma Penumathsa ◽  
Srikanth Koneru ◽  
Mahesh Thirunavukkarasu ◽  
Lijun Zhan ◽  
Nilanjana Maulik
Keyword(s):  
Left Ventricle ◽  
Western Blot ◽  
Infarct Size ◽  
Blot Analysis ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Thioredoxin 1 ◽  
Lac Z

Hypertension the major risk factor for many cardiovascular diseases is a result of multiple causes along with excessive generation of reactive oxygen species resulting in imbalance of redox status. Thioredoxin-1 (Trx-1) is a redox regulatory multifunctional protein with anti-inflammatory, anti-apoptotic and antioxidant effects. In the present study we investigated the therapeutic potential of Adeno-Trx-1 in spontaneously hypertensive rats (SHR). The rats were assigned to four different groups (n = 24) such as (1) normotensive Wistar Kyoto (WKY) (2) SHR (3) SHR +Adeno-Lac-Z (SHRLac-Z) and (4) SHR +Adeno-Trx-1 (SHRTrx-1). Echo-guided gene delivery to the anterior wall of left ventricle was performed using 1x109 pfu of adenovirus constructed with Trx-1 and Lac-Z. Two days after injection of adeno virus, the hearts were subjected to permanent left anterior descending coronary artery occlusion (MI). Left ventricular functions by Echocardiography were examined after 30 days of MI as the significant changes in left ventricle were observed after 4 weeks of MI. Decreased left ventricular inner diameter (7 vs 9 mm) and increased ejection fraction (52 vs 42 %), fractional shortening (28 vs 22 %) was observed in SHRTrx-1 compared to SHR. Infarct size, cardiomyocyte apoptosis and protein expression profiles (by Confocal and Western blot analysis) were observed at predetermined time points i.e after 24 and 48 hours of MI respectively. Decreased infarct size (52% vs 67%), cardiomyocyte apoptosis by TUNEL assay (161 vs 240) and increased expression of Trx-1 and HO-1 were observed in SHRTrx-1 compared to SHR. Confocal results were also confirmed by Western blot analysis. Results documented increased expression of Trx-1 (1.8 fold) and HO-1 (1.4 fold) in SHRTrx-1 as compared to SHR. In addition, we have also observed increased expression of anti-apoptotic protein Bcl-2 (1.7 fold) in SHRTrx-1 treated group compared SHR. Thus our results demonstrate for the first time that the cardioprotective effect of Adeno-Trx-1 therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent a novel mechanism for therapy against hypertension induced post infarction heart failure.

Enalapril attenuates cardiorenal damage in nitric-oxide-deficient spontaneously hypertensive rats

2004 ◽  
Vol 106 (3) ◽  
pp. 337-343 ◽  
Author(s):  
Leila M. M. PEREIRA ◽  
Daniele G. BEZERRA ◽  
Denise L. MACHADO ◽  
Carlos A. MANDARIM-DE-LACERDA
Keyword(s):  
Nitric Oxide ◽  
Body Mass ◽  
Structural Damage ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Genetic Hypertension ◽  
Lv Mass ◽  
Significant Difference

Stereological structural alterations of the heart and kidney were studied in four groups (n=5) of spontaneously hypertensive rats (SHRs) treated for 30 days: (i) control, (ii) NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthesis inhibitor] alone, (iii) enalapril alone and (iv) L-NAME plus enalapril. Blood pressure (BP) was elevated significantly in NO-deficient SHRs (rats receiving L-NAME) or significantly lower in enalapril-treated SHRs. Co-administration of L-NAME and enalapril caused a 20% decrease in BP compared with untreated SHRs. NO-deficient SHRs had a decrease in body mass, but this loss of body mass was prevented efficiently in the enalapril-treated group. Enalapril treatment decreased the left ventricular (LV) mass index in SHRs, even in animals with NO synthesis blocked. NO deficiency in SHRs caused a larger decrease in the number of LV cardiomyocyte nuclei, which had a negative correlation with both LV mass index and BP. The volume-weighted glomerular volume (VWGV) separated the SHRs into two groupings: (i) control and NO-deficient SHRs, and (ii) enalapril- and L-NAME plus enalapril-treated SHRs. There was a significant difference between these two groupings, with VWGV being more than 15% smaller in the latter compared with the former grouping. The present findings reinforce the evidence that enalapril efficiently treats genetic hypertension, and demonstrate that this effect is observed even when NO synthesis is inhibited. Enalapril administration also decreases cardiac and renal structural damage caused by genetic hypertension, as well as by the interaction between genetic hypertension and NO deficiency.

Effect of chlorothiazide on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats

1985 ◽  
Vol 69 (5) ◽  
pp. 511-515 ◽  
Author(s):  
P. J. O. Manhem ◽  
S. A. Clark ◽  
W. B. Brown ◽  
G. D. Murray ◽  
J. I. S. Robertson
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Tap Water ◽  
Treated Group ◽  
Temporal Association ◽  
Control Group ◽  
Exchangeable Sodium ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

1. Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. 2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. 3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. 4. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. 5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. 6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. 7. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. 8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. 9. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.

Abstract 363: Recovery of Exercise Intolerance and Ventricular Dysfunction of Infarcted Spontaneously Hypertensive Rats After Oral Treatment With an Agonist of Adenosine Receptor

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jaqueline S da Silva ◽  
Roberto T Sudo ◽  
Roberto Debom ◽  
Eliezer J Barreiro ◽  
Carlos A Fraga ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Ventricular Dysfunction ◽  
Diastolic Pressure ◽  
Oral Treatment ◽  
Treated Group ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Positive Staining ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Severe ventricular dysfunction is observed in spontaneously hypertensive rats (SHR) submitted to myocardial infarction (MI). The present work evaluates the cardioprotective effects of oral administration of a novel agonist of adenosine A2A receptor, LASSBio-294, in infarcted SHR. Methods: Male SHR (12-14 wks old) were randomly divided into groups: sham and infarcted (MI) which were either treated orally with vehicle or LASSBio-294 (10 mg/kg) for 28 days. Before and after the animals were treated with LASSBio-294, cardiac function and exercise capacity were evaluated through the echocardiography and treadmill test. Mean blood pressure (MBP), left ventricular end diastolic pressure (LVEDP) and negative dP/dt were also determined. Fibrosis in heart sections were detected using H&E staining. Immunohistochemical staining for TNF-alpha and SERCA2a in LV tissues were observed. Results: MI in SHR reduced the running distance from 257.9 ± 13.2 to 39.0 ± 4.4 m which normalized to 296.0 ± 26.4 m after treatment with LASSBio-294. Reduced anterior wall thickness was observed after MI (0.51 ± 0.14 mm) which was prevented with treatment (1.65 ± 0.21 mm). Ratio of early and late transmitral filling velocity was reduced from 1.48 ± 0.09 to 0.99 ± 0.04 and recovered to 1.35 ± 0.07 after treatment. MBP was reduced from 169.0 ± 5.6 to 120.4 ± 7.4 mmHg in SHR-IM treated with LASSBio-294. Increased LVEDP of 25.6 ± 3.2 observed in SHR-IM was reduced to 7.3 ± 1.0 mmHg after treatment. The -dP/dt was reduced in SHR-MI to -5698 ± 408.1 mmHg/s and returned to -7894 ± 631.6 mmHg/s after LASSBio-294 treatment. There was an increase in collagen deposition after MI (from 14.5 ± 3.5 to 59.8 ± 5.4 %) which was prevented with LASSBio-294 treatment (29.5 ± 2.2 %). Increase of positive staining for TNF-α was observed in SHR-MI (from 9.5 ± 1.0 to 32.3 ± 2.1%) which recovered in SHR-MI treated group (14.4 ± 1.3%). Also, the expression of SERCA2a was reduced in ventricular muscle from SHR-IM (from 68.7 ± 5.1 to 21.4 ± 2.3 %) which partially recovered to 40.6 ± 1.19% with LASSBio-294 treatment. Conclusion: LASSBio-294 reduced exercise intolerance, prevented cardiac remodeling and diastolic dysfunction in infarcted SHR.

Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats

2007 ◽  
Vol 293 (4) ◽  
pp. H2093-H2100 ◽  
Author(s):  
Ying-Xian Shi ◽  
Ying Chen ◽  
Yi-Zhun Zhu ◽  
Guo-Ying Huang ◽  
Philip Keith Moore ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Conjugated Diene ◽  
Hypertensive Rats ◽  
Sodium Hydrosulfide ◽  
Spontaneously Hypertensive ◽  
Base Modification ◽  
Dna Base ◽  
Cardioprotective Effects

Hydrogen sulfide (H2S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H2S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 μmol·kg−1·day−1), a combination of NaHS (30 μmol·kg−1·day−1) and glibenclamide (5 mg·kg−1·day−1), glibenclamide alone (5 mg·kg−1·day−1), hydralazine alone (10 mg·kg−1·day−1), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 μm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.

scholarly journals Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats

2008 ◽  
Vol 23 (2) ◽  
pp. 173-178 ◽  
Author(s):  
Nilo César do Vale Baracho ◽  
Guilherme D'Andréa Saba Arruda ◽  
Lidinei José Alves ◽  
Márcio Felipe Salomon Carneiro ◽  
Matheus Teodoro Grilo Siqueira ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Systemic Disease ◽  
Control Group ◽  
High Morbidity ◽  
Hypertensive Rats ◽  
Reference Drug ◽  
Spontaneously Hypertensive ◽  
Enalapril Maleate ◽  
Significant Difference

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.

scholarly journals High-calorie diet influence on morphological and functional parameters of the cardiovascular system in spontaneously hypertensive rats

2021 ◽  
Vol 10 (1) ◽  
pp. 50-57
Author(s):  
A.Yu. Ivanova ◽  
◽  
E.Yu. Rysenkova ◽  
M.A. Afanasiev ◽  
P.V. Chumachenko ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Spontaneously Hypertensive Rats ◽  
Myocardial Hypertrophy ◽  
Left Ventricular ◽  
Control Group ◽  
Chow Diet ◽  
Standard Diet ◽  
High Fat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Introduction. Hypertension with left ventricular hypertrophy (LVH) is a major independent risk factor for cardiovascular-related morbidity. Diet plays an essential role in the prevention and treatment of chronic cardiovascular disease. The aim of our study was to analyze the influence of 10-week diets consisting of different high fats and carbohydrates on the myocardium in spontaneously hypertensive rats (SHR). Materials and methods. The SHR (n=34) and WKY (n=34) were randomly divided into five groups (n=6 or 7 per group). For 10 weeks, the control group was fed the standard diet; the experimental groups were fed the standard chow diet with the different fats and sucrose (11% of the calorie intake). Systolic blood pressure (SBP) was measured before the experiment and 10 weeks after by the non-invasive tail-cuff method. After the experiment, the animals were humanely sacrificed. The heart specimens after routine processing were stained with hematoxylin and eosin. We determined the thickness of the left ventricle and the number of cardiomyocyte nuclei per unit area using morphometry. Results. An increase in SBP at the end of the experiment was found in SHR animals in groups receiving trans-fat and sucrose by 10.9 mm Hg and 13.4 mm Hg, respectively. Myocardial hypertrophy was observed in the SHR Butter group. Conclusion. We found that the increased content of trans-fats and sucrose in the diet leads to an increase in SBP in spontaneously hypertensive rats; saturated fatty acids – to myocardial hypertrophy in spontaneously hypertensive rats without aggravation of systolic hypertension. In normotensive animals, no negative effect of the high-fat diet on the cardiovascular system was observed. Keywords: myocardial hypertrophy, arterial hypertension, high fat diets, palm oil, carbohydrates

scholarly journals Antihypertensive and Renal Protective Effects of Oryeongsan in Spontaneously Hypertensive Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kiwan Kang ◽  
Minjeong Jeong ◽  
Hongjun Kim ◽  
Beomjin Lim ◽  
Sangjun Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Treated Group ◽  
Renal Tissue ◽  
Quality Data ◽  
Protective Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Significant Difference ◽  
History Of Use

Oryeongsan (ORS), a traditional medicine used to regulate body fluids, has a long history of use as a diuretic in Korea, China, and Japan. ORS is commonly thought to lower blood pressure, but high-quality data on its effects are sparse. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP). Then, 10 mL/kg of vehicle (distilled water) or 200 mg/kg of ORS extract were administered orally once a day for 3 weeks. SBP and DBP were measured at weeks 1, 2, and 3. At the end of the experiment, blood was collected, and kidneys were removed for histology. By the 2nd and 3rd week after initiation of treatment, the ORS-treated group had significantly lower SBP than control-treated rats (191.3 ± 6.5 vs. 206.3 ± 9.8 mmHg, p  = 0.022 at the 2nd week; 195.8 ± 7.8 vs. 217.0 ± 8.1 mmHg, p  = 0.003 at the 3rd week, respectively). The ORS-treated group trended toward having a lower DBP than control, but there was no significant difference. Blood urea nitrogen (BUN) and serum creatinine (Cr) were not different between the ORS-treated and control groups (BUN: 23.7 ± 1.1 vs. 22.7 ± 2.8 mg/dL, p  = 0.508; Cr: 19.0 ± 2.2 vs. 21.6 ± 2.1 μM, p  = 0.083, respectively). The percentage of renal tissue affected by tubulointerstitial fibrosis was significantly lower in the ORS-treated group (1.68 ± 0.60) compared to controls (3.17 ± 0.96, p  = 0.019). These findings suggest that treatment with ORS reduces SBP and ameliorates renal damage in SHR.

scholarly journals Progressive Myocardial Apoptosis and Cardiac Dysfunction in Spontaneously Hypertensive Rats During Aging

2020 ◽  
Vol 33 (2) ◽  
pp. 205-205
Author(s):  
Yun Wu ◽  
Li-yun Fu ◽  
Qin-yun Ruan ◽  
Lei Yan ◽  
Chun-yan Huang ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Myocardial Apoptosis ◽  
Significant Difference ◽  
Related Proteins

Abstract Objective To investigate myocardial apoptosis and the expression of apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) and Bax], cardiac hypertrophy, and function in spontaneously hypertensive rats (SHR) during aging. Methods Male SHR (n = 36) and Wistar-Kyoto rats (WKY, n = 30) were monitored for their cardiac function from 14 to 102 weeks of age using echocardiography. Myocardial apoptosis in the subendocardium and subepicardium was analyzed using TUNEL staining. The apoptosis-related proteins (Bcl-2 and Bax) were assessed by Western blot analysis. Results Left ventricular mass index (LVMI) in SHR increased progressively with age. Left ventricular ejection fraction (LVEF) showed no significant difference from 14 to 66 weeks of age, but decreased significantly in SHR from 84 to 102 weeks of age. The apoptotic index (APOI) of myocardial cells in SHR increased with age, in which subendocardial APOI (APOI-endo) increased at 66 weeks and was significantly higher than the age-matched WKY (9.83 ± 3.97 vs. 4.03 ± 2.06, P < 0.05). Additionally, the subepicardial APOI (APOI-epi) increased significantly at 84 weeks of age (P < 0.05). Bax/Bcl-2 ratio was higher in SHR than WKY at 66 weeks (3.98 ± 0.80 vs. 0.29 ± 0.06, P < 0.05), and enhanced further at 102 weeks of age (10.54 ± 1.60 vs. 0.70 ± 0.13, P < 0.05). Myocardial APOI was positively correlated with LVMI (r = 0.83, P < 0.01), negatively with LVEF in 66–102 weeks (r = −0.81, P < 0.01), and positively with Bax/Bcl-2 ratio (r = 0.79, P < 0.01). Conclusion Myocardial apoptosis increases with aging and is associated with progressive left ventricular remodeling and cardiac dysfunction in SHR.

Effects of Chronic Eta-Receptor Blockade in Stroke-Prone Spontaneously Hypertensive Rats.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 699-700
Author(s):  
Christine Elise Barandier ◽  
Zhihong Yang ◽  
Thomas Felix Luscher
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Treated Group ◽  
The Body ◽  
Cerebral Injury ◽  
Control Group ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Eta Receptor

P38 It has been reported that some ET-receptor blockers prevent cerebral injury in stroke-prone spontaneously hypertensive rats (SPSHR), whereas chronic inhibition of nitric oxide synthase (NOS) precipitates stroke. We investigated the protective effects of chronic treatment with BSF208075, a selective ETA-receptor blocker in SPSHR treated with the NOS inhibitor, L-NAME, or untreated. 4 groups of male SPSHR, 10 week old, were studied: a control group and 3 groups treated with BSF208075 (30 mg/kg/day), L-NAME (10 mg/kg/day) or BSF208075+L-NAME (30 and 10 mg/kg/day, respectively). Systolic blood pressure, body weight and survival were recorded. In the control group, severe hypertension (292.3±1.0mmHg; p<0.01 vs baseline) developed within 4 weeks. In contrast, in the BSF208075-treated group, the development of hypertension (265.2±3.8mmHg; p<0.01 vs control) was limited and blood pressure started to decrease after 4 weeks of treatment. In both of these groups, the increase in body weight was normal and similar, and 90% of the animals were still alive after 50 days of treatment. In the L-NAME-treated group, the blood pressure immediately and drastically increased, the body weight was reduced by 50% within 6 weeks of treatment. 50% of mortality was observed after 22 days of treatment, and all rats died within 36 days. The mean survival was 25.9±2.4 days. In L-NAME+BSF208075-treated group, BSF208075, although it did not prevent the development of hypertension, it reduced the loss of body weight and increased mean survival to 36.7±1.4 days (p<0.01 vs L-NAME-treated group). In this group, 50% of mortality was observed after 37 days of treatment, and all rats died within 41 days. These results show that BSF208075 delays the development of hypertension in SPSHR, and increases survival of L-NAME-treated SPSHR, independent of hypertension.

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