Open AccessValsartan ameliorates ageing‐induced aorta degeneration via angiotensin II type 1 receptor‐mediated ERK activity
Author(s) -
Shan HaiYan,
Zhang Siyang,
Li Xuelian,
yu Kai,
Zhao Xin,
Chen Xinyue,
Jin Bo,
Bai XiaoJuan
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.12251
Subject(s) - valsartan , mapk/erk pathway , ageing , angiotensin ii , receptor , kinase , medicine , endocrinology , blot , pharmacology , chemistry , biology , microbiology and biotechnology , biochemistry , blood pressure , gene
Angiotensin II (Ang II) plays important roles in ageing‐related disorders through its type 1 receptor ( AT 1 R). However, the role and underlying mechanisms of AT 1R in ageing‐related vascular degeneration are not well understood. In this study, 40 ageing rats were randomly divided into two groups: ageing group which received no treatment (ageing control), and valsartan group which took valsartan (selective AT 1R blocker) daily for 6 months. 20 young rats were used as adult control. The aorta structure were analysed by histological staining and electron microscopy. Bcl‐2/Bax expression in aorta was analysed by immunohistochemical staining, RT ‐ PCR and Western blotting. The expressions of AT 1 R, AT 2 R and mitogen‐activated protein kinases ( MAPK s) were detected. Significant structural degeneration of aorta in the ageing rats was observed, and the degeneration was remarkably ameliorated by long‐term administration of valsartan. With ageing, the expression of AT 1R was elevated, the ratio of Bcl‐2/Bax was decreased and meanwhile, an important subgroup of MAPK s, extracellular signal‐regulated kinase ( ERK ) activity was elevated. However, these changes in ageing rats could be reversed to some extent by valsartan. In vitro experiments observed consistent results as in vivo study. Furthermore, ERK inhibitor could also acquire partial effects as valsartan without affecting AT 1R expression. The results indicated that AT 1R involved in the ageing‐related degeneration of aorta and AT 1R‐mediated ERK activity was an important mechanism underlying the process.