Original ArticleIsosorbide Dinitrate Inhibits Mechanical Stress-induced Cardiac Hypertrophy and Autophagy Through Downregulation of Angiotensin II Type 1 ReceptorLin, Li MD, PhD*; Xu, Jianfeng MD, PhD†; Ye, Yong MD, PhD†; Ge, Junbo MD†; Zou, Yunzeng MD, PhD, FAHA†; Liu, Xuebo MD, PhD*Author Information *Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China; and †Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan University, Shanghai, China. Reprints: Xuebo Liu, MD, PhD, Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Shanghai 200120, China (e-mail: [email protected]). Supported by the National Natural Science Foundation of China (81100145, 81300082), the National Science Foundation for Post-doctoral Scientists of China (2013M531124), the Science and Technology Commission of Shanghai Municipality (12ZR1425100), and the Chinese Medical Doctor Association (DFCMDA201255, DFCMDA201259). The authors report no conflicts of interest. Received December 02, 2013 Accepted April 20, 2014 Journal of Cardiovascular Pharmacology: January 2015 - Volume 65 - Issue 1 - p 1-7 doi: 10.1097/FJC.0000000000000122 Buy Metrics Abstract Abstract: Mechanical stress can induce cardiac hypertrophy and autophagy. Recently, it has been reported that nitric oxide donors inhibited autophagy in human chondrocytes. Therefore, the effect of isosorbide dinitrate (ISDN) on cardiac hypertrophy and autophagy induced by mechanical stress was investigated in this study. A 48-hour mechanical stretch and a 4-week transverse aortic constriction were performed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, before the assessment of myocardial autophagy using LC3b-II. ISDN was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Furthermore, mechanical stress was shown to upregulate angiotensin II (AngII) type 1 (AT1) receptor expression in both cultured cardiomyocytes and in mouse hearts, whereas ISDN was demonstrated to significantly suppress the upregulation of the AT1 receptor. It was concluded that ISDN could inhibit mechanical stress-induced cardiac hypertrophy and autophagy through the downregulation of AT1 receptor expression. © 2015 by Lippincott Williams & Wilkins.