scholarly journals mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats

2021 ◽  
Author(s):  
Jianshu Chen ◽  
Jing Yu ◽  
Ruowen Yuan ◽  
Ningyin Li ◽  
Caie Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Postmenopausal Women ◽  
Signaling Pathway ◽  
Mtor Inhibitor ◽  
Myocardial Hypertrophy ◽  
The Other ◽  
Female Rats ◽  
Myocardial Tissue ◽  
Hypertensive Rats

Compelling evidence have described the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team’s previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mTOR signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly im) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8mg/kg/day Vs 1.5mg/kg/day Vs 2mg/kg/day ip) in OVX+ estrogens(E 9.6 mg/Kg/day, ig)+T group was further evaluated. After T intervention, the OVX female rats exhibited significant increments in the heart weight / tibial length (TL), area of cardiomyocytes and the mRNA expressions of atrial natriuretic peptide, β- myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and issue inhibitor of metalloproteinase 1. Mammalian rapamycin receptor (mTOR), ribosomal protein S6 kinase (S6K1),4E-bindiong protein 1(4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX+E+T group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of T-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/ S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high T levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate T-induced cardiomyocyte hypertrophy

scholarly journals Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats

2006 ◽  
Vol 21 (4) ◽  
pp. 192-196 ◽  
Author(s):  
José Ricardo Sousa Ayres de Moura ◽  
Nelson Sass ◽  
Sérgio Botelho Guimarães ◽  
Paulo Roberto Leitão de Vasconcelos ◽  
Rosiane Mattar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Statistical Significance ◽  
Virgin Female ◽  
Female Rats ◽  
Vaginal Smear ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Oral Supplementation

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 p<0.05. RESULTS: There was no significant weight gain in isolated L-arginine treated SHR. Mean blood pressure decreased in L-arginine-treated SLR compared with untreated-SHR rats. CONCLUSION: L-arginine oral supplementation reduces blood pressure in spontaneously hypertensive rats during pregnancy.

scholarly journals β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Catherina A. Cuevas ◽  
Cheril Tapia-Rojas ◽  
Carlos Cespedes ◽  
Nibaldo C. Inestrosa ◽  
Carlos P. Vio
Keyword(s):  
Blood Pressure ◽  
Signal Transduction ◽  
Single Dose ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Target Genes ◽  
Hypertensive Rats ◽  
Collagen Types ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect. Sinceβ-catenin signal transduction participates in fibrotic processes, we evaluated the contribution ofβ-catenin-dependent signaling pathway in hypertension-induced renal fibrosis. Two-kidney one-clip (2K1C) hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3 days for 2 weeks). The treatment with lisinopril reduced the systolic blood pressure from 220 ± 4 in 2K1C rats to 112 ± 5 mmHg (P<0.05), whereas the reduction in blood pressure with pyrvinium pamoate was not significant (212 ± 6 in 2K1C rats to 170 ± 3 mmHg,P>0.05). The levels of collagen types I and III, osteopontin, and fibronectin decreased in the unclipped kidney in both treatments compared with 2K1C rats. The expressions ofβ-catenin, p-Ser9-GSK-3beta, and theβ-catenin target genes cyclin D1, c-myc, and bcl-2 significantly decreased in unclipped kidney in both treatments (P<0.05). In this study we provided evidence thatβ-catenin-dependent signaling pathway participates in the renal fibrosis induced in 2K1C rats.

Abstract 9: Endothelin B Receptors Protect Against Hypertension Induced by Chronic Angiotensin II in Female Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Wararat Kittikulsuth ◽  
David M Pollock
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Male And Female ◽  
Male And Female Rats ◽  
Endothelin B

Endothelin B (ET B ) receptors mediate vasodilation, anti-inflammation and natriuresis, which ultimately contribute to blood pressure control. We previously showed that renal medullary ET B receptor function is maintained in female angiotensin (Ang) II hypertensive rats, while male Ang II hypertensive rats have blunted ET B -induced natriuretic responses. Because female rats are more resistance to blood pressure elevation induced by high salt intake and/or Ang II infusion, we hypothesized that ET B receptors protect female rats against the hypertensive response and renal injury induced by a high salt diet and chronic Ang II infusion compared to males. Male and female rats received Ang II infusion (150 ng/kg/min; sc.) with 4% NaCl for 4 weeks; blood pressure was measured by telemetry. After a week of Ang II infusion with a high salt diet, subsets of both male and female rats received the ET B antagonist, A-192621, at three doses on consecutive weeks (1, 3, and 10 mg/kg/d in food). Male rats had a significantly higher blood pressure compared to females after 4 weeks of Ang II (178±10 vs. 138±10 mmHg; p<0.05). A-192621 resulted in a dose-dependent increase in blood pressure in female Ang II hypertensive rats (167±8 mmHg at 10 mg/kg/d; p<0.05); the increase produced by A-192621 in male Ang II hypertensive rats was not statistically significant (193±10 mmHg). After 4 weeks of Ang II infusion, the level of proteinuria and nephrinuria was higher in male rats compared to female. A-192621 did not further increase urinary excretion of protein or nephrin in both male and female Ang II hypertensive rats. In conclusion, these results support the hypothesis that ET B receptors provide more protection against hypertension during chronic Ang II infusion in female rats compared to male.

Regression of myocardial hypertrophy and influence of adrenergic system

1983 ◽  
Vol 244 (1) ◽  
pp. H97-H101 ◽  
Author(s):  
S. Sen ◽  
R. C. Tarazi
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Regression Analysis ◽  
Arterial Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Myocardial Hypertrophy ◽  
Cardiac Response ◽  
Adrenergic System ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Studies of regression of myocardial hypertrophy in spontaneously hypertensive rats (SHR) suggest that the adrenergic system may play an important role in the reversal of hypertrophy. The effect of propranolol on reversal of hypertrophy, however, is still controversial. This study describes the effect of propranolol, given alone or in combination with hydralazine in different ratios for 4 wk, on blood pressure (BP), ventricular weight, and myocardial catecholamine (MC) concentrations. The data show that a certain ratio of propranolol to hydralazine (750:30) leads to moderate BP control (196-156 mmHg) without increased MC (634 vs. 552 ng/g) and moderately reduced hypertrophy. Reduction of BP alone with increased MC (hydralazine alone) or reduction of MC without BP control (propranolol alone) failed to reduce hypertrophy. A significant correlation between both ventricular weight and heart rate with MC (r = 0.6) was obtained by multiple regression analysis. This study suggests that adrenergic factors seem to play an important role in modulating structural cardiac response to variations in arterial pressure.

scholarly journals The Effects of Aqueous Extract from Nardostachys chinensis Batalin on Blood Pressure and Cardiac Hypertrophy in Two-Kidney One-Clip Hypertensive Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Rayile Aisa ◽  
Zhaoxia Yu ◽  
Xiangyang Zhang ◽  
Dilinuer Maimaitiyiming ◽  
Lipeng Huang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Aqueous Extract ◽  
Caspase 3 ◽  
Left Ventricular ◽  
Left Renal Artery ◽  
Hypertensive Rats ◽  
Left Ventricular Tissue ◽  
Nardostachys Chinensis ◽  
Ventricular Tissue

Aims. The aim of this study was to investigate the effects of the aqueous extract of Nardostachys chinensis Batalin (NCBAE) on blood pressure and cardiac hypertrophy using two-kidney one-clip (2K1C) hypertensive rats. Methods. 2K1C rat models were set up by clipping the left renal artery. Sham-operated rats underwent the same surgical procedure except for renal arterial clipping. 2K1C hypertensive rats were orally given NCBAE at doses of 210, 420, and 630 mg·kg−1·d−1 for 6 weeks. Twelve weeks after surgery, rat SBP and echocardiographic parameters were measured, cardiac histopathology was assessed, serum NO and LDH were detected, and the expression of Bcl-2 and caspase-3 of left ventricular tissue was assessed by western blot. Results. Treatment with NCBAE resulted in a decrease of SBP, LVPWd, LVPWs, IVSd, IVSs, LVW/BW ratio, and cardiomyocyte CSA, an increase of LVEF, and inhibition of 2K1C-induced reduction in serum NO and elevation of LDH compared with 2K1C group. NCBAE intervention also showed a significant increase of Bcl-2 expression and reduction of cleaved caspase-3 level dose-dependently in left ventricular tissue. Conclusion. Our data demonstrate that NCBAE has an antihypertensive property and protective effect on 2K1C-induced cardiac hypertrophy especially at the dose of 630 mg·kg−1·d−1.

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