title: Isosorbide dinitrate inhibits mechanical stress-induced cardiac hypertrophy and autophagy through downregulation of angiotensin II type 1 receptor.
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.
authors.affiliation: *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.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D013314:Stress, Mechanical
chemical_list: D044140:Receptor, Angiotensin, Type 1; D007548:Isosorbide Dinitrate