Resveratrol inhibits right ventricular hypertrophy induced by monocrotaline in rats.
1. Resveratrol (RSV), a polyphenol in red wine, exhibits cardioprotective effects in vitro, such as inhibition of angiotensin II- or phenylephrine-induced cardiomyocyte hypertrophy in rat neonatal myocyte cultures and suppression of cardiac fibroblast proliferation. The aim of the present study was to investigate the protective effects of RSV against monocrotaline (MCT)-induced right ventricular (RV) hypertrophy in rats. 2. Male Sprague-Dawley rats were given a single injection of MCT (50 mg/kg, s.c.) and were then treated with either vehicle (normal saline) or RSV (10 and 30 mg/kg, i.g., twice daily) for 21 days. A separate group of control rats were not injected with MCT and were treated with normal saline for 21 days. At the end of the treatment period, all rats were subjected to echocardiography and haemodynamic measurements. In addition, after rats had been killed, the hearts were subjected to histopathological, untrastructural and immunohistochemical analyses. 3. In vehicle-treated rats, MCT injection resulted in 33% mortality, whereas mortality in RSV-treated MCT-injected rats was 0%. In vehicle-treated rats, MCT increased RV free wall thickness and RV systolic pressure and decreased pulmonary arterial acceleration time at the end of the experimental period. These dynamic changes were ameliorated by RSV in a dose-dependent manner. Histologically, MCT injection resulted in RV hypertrophy, swollen mitochrondria and cardiomyocyte apoptosis; all these morphological changes were dose-dependently improved in rats treated with RSV. 4. In conclusion, RSV inhibits the RV hypertrophy induced by MCT in rats and this effect is mediated by both a direct effect of RSV on cardiomyocytes and an indirect effect mediated via a reduction in pulmonary hypertension.
Yang
Dan-Li
DL
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Institute of Materia Medica, Chongqing, China.
Zhang
Hai-Gang
HG
Xu
Ya-Li
YL
Gao
Yun-Hua
YH
Yang
Xiao-Jiao
XJ
Hao
Xue-Qin
XQ
Li
Xiao-Hui
XH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
D002316:Cardiotonic Agents; D013267:Stilbenes; D016686:Monocrotaline; D000077185:Resveratrol