Open AccessAliskiren‐attenuated myocardium apoptosis via regulation of autophagy and connexin‐43 in aged spontaneously hypertensive rats
Author(s) -
Zhang Wenbin,
Zhao Gang,
Hu Xiaona,
Wang Min,
Li Hua,
Ye Yong,
Du Qijun,
Yao Jin,
Bao Zhijun,
Hong Wei,
Fu Guosheng,
Ge Junbo,
Qiu Zhaohui
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12273
Subject(s) - aliskiren , atg5 , apoptosis , autophagy , endocrinology , medicine , tunel assay , renin–angiotensin system , chemistry , blood pressure , immunohistochemistry , biochemistry
There are controversies about the mechanism of myocardium apoptosis in hypertensive heart disease. The aim of this study was to investigate the relationship among autophagy, Cx43 and apoptosis in aged spontaneously hypertensive rats ( SHR s) and establish whether A liskiren is effective or not for the treatment of myocardium apoptosis. Twenty‐one SHR s aged 52 weeks were randomly divided into three groups, the first two receiving A liskiren at a dose of 10 and 25 mg/kg/day respectively; the third, placebo for comparison with seven W istar‐ K yoto ( WKY ) as controls. After a 2‐month treatment, systolic blood pressure ( SBP ), heart to bw ratios ( HW / BW %) and angiotensin II (AngII) concentration were significantly enhanced in SHR s respectively. Apoptotic cardiomyocytes detected with TUNEL and immunofluorescent labelling for active caspase‐3 increased nearly fourfolds in SHR s, with a decline in the expression of survivin and AKT activation, and an increase in caspase‐3 activation and the ratio of Bax/Bcl‐2. Myocardium autophagy, detected with immunofluorescent labelling for LC 3‐II, increased nearly threefolds in SHR s, with the up‐regulation of Atg5, Atg16L1, Beclin‐1 and LC 3‐II. The expression of Cx43 plaque was found to be down‐regulated in SHR s. Aliskiren significantly reduced SBP , HW / BW %, AngII concentration and the expression of AT 1 R. Thus, Aliskiren protects myocardium against apoptosis by decreasing autophagy, up‐regulating Cx43. These effects showed a dose‐dependent tendency, but no significance. In conclusion, the myocardium apoptosis developed during the hypertensive end‐stage of SHR s could be ameliorated by Aliskiren via the regulation of myocardium autophagy and maladaptive remodelling of Cx43.