title: Resveratrol Ameliorates Pressure Overload-induced Cardiac Dysfunction and Attenuates Autophagy in Rats.
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.
authors.affiliation: *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.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Wang
authors.forename: Mengxi
authors.initials: M
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Yang
authors.forename: Jinghe
authors.initials: J
authors.lastname: Sun
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiwen
authors.initials: X
authors.lastname: Huang
authors.forename: Tianhui
authors.initials: T
authors.lastname: Yuan
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Shen
authors.forename: Shaoxiang
authors.initials: S
authors.lastname: Xian
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006334:Heart Function Tests; D006973:Hypertension / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D013267:Stilbenes; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol