Resveratrol ameliorates pressure overload-induced cardiac dysfunction and attenuates autophagy in rats.
J Cardiovasc Pharmacol. 2015 Jul 7. Epub 2015 Jul 7. PMID: 26167810
Pressure overload has an important role in heart failure, inducing excessive autophagy in cardiac myocytes that is considered to be pathogenic. Resveratrol has been reported to improve cardiac dysfunction induced by pressure overload, but it has been unclear whether resveratrol ameliorates cardiac dysfunction by regulating autophagy. In this study, heart failure was induced in rats by constriction of the abdominal aorta. Four weeks after surgery, the rats with heart failure were randomized to treatment with resveratrol (8 mg/kg/d by intraperitoneal injection) for 28 days or to intraperitoneal injection of the vehicle (propylene glycol) alone. Echocardiography was performed to assess cardiac function. Expression of BNP mRNA in the left ventricle was detected by real-time PCR, while expression of proteins associated with autophagy (beclin-1 and lamp-1) was detected by western blotting and immunohistochemistry. Furthermore, autophagic vacuoles were detected in the heart by transmission electron microscopy and the myocardial ATP content was measured by the bioluminescence method. Treatment with resveratrol significantly improved cardiac dysfunction and reduced BNP expression in rats with heart failure. Resveratrol downregulated beclin-1 and lamp-1 expression, and also inhibited the formation of autophagic vacuoles in failing hearts. Furthermore, resveratrol restored the myocardial ATP level and reduced phosphorylation of AMP-activated protein kinase (AMPK) at Thr172. These results suggest that resveratrol may inhibit autophagy through inactivation of AMPK and restoration of ATP in heart failure induced by pressure overload. Accordingly, resveratrol may be beneficial for patients with hypertensive heart disease.