Original ArticleResveratrol Ameliorates Pressure Overload–induced Cardiac Dysfunction and Attenuates Autophagy in RatsWang, Lingjun MD, PhD*,†; Gao, Mengxi MD*; Chen, Jie MD, PhD*; Yang, Zhongqi MD, PhD*; Sun, Jinghe MD, PhD*; Wang, Zhaohui MD, PhD*; Huang, Xiwen MD, PhD*; Yuan, Tianhui MD, PhD*; Shen, Xiaoxiao MD*; Xian, Shaoxiang MD, PhD*,†Author Information *The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; and †Laboratory of Chinese Internal Medicine, National Key Disciplines, Guangzhou University of Chinese Medicine, Guangzhou, China. Reprints: Shaoxiang Xian, MD, PhD, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China (e-mail: [email protected]). Supported by the National Natural Science Foundation of China (grant nos. 81102585, 81173438, and 81373570), the China Postdoctoral Science Foundation (grant no. 20110490871), and the Natural Science Foundation of Guangdong Province (grant no. S2011040003510). The Young Talents Program of Guangzhou University of Chinese Medicine (grant no. 20140115). The authors report no conflicts of interest. Received April 03, 2015 Accepted June 10, 2015 Journal of Cardiovascular Pharmacology: October 2015 - Volume 66 - Issue 4 - p 376-382 doi: 10.1097/FJC.0000000000000290 Buy Metrics Abstract 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−1·d−1 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 brain natriuretic peptide messenger RNA in the left ventricle was detected by real-time polymerase chain reaction, whereas 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 brain natriuretic peptide expression in rats with heart failure. Resveratrol down-regulated 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 at Thr172. These results suggest that resveratrol may inhibit autophagy through inactivation of AMP-activated protein kinase and restoration of ATP in heart failure induced by pressure overload. Accordingly, resveratrol may be beneficial for patients with hypertensive heart disease. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.