MISC

2007年4月

Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
  • Guo-Xing Zhang
  • ,
  • Koji Ohmori
  • ,
  • Yukiko Nagai
  • ,
  • Yoshihide Fujisawa
  • ,
  • Akira Nishiyama
  • ,
  • Youichi Abe
  • ,
  • Shoji Kimura

42
4
開始ページ
804
終了ページ
811
記述言語
英語
掲載種別
DOI
10.1016/j.yjmcc.2007.01.012
出版者・発行元
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

Elevated activities of the sympathetic nerve and renin-angiotensin systems are common features of heart failure. This study was designed to investigate the roles of the AT1 receptor in cardiac hypertrophy and oxidative stress during excessive beta-adrenoceptor stimulation using an AT1 receptor antagonist (ARB) and AT1a receptor-deficient (AT1aR(-/-)) mice. Isoproterenol (ISO) was given to C57BL mice with or without ARB (olmesartan) treatment and to AT1aR(-/-) mice by a subcutaneously implanted osmotic mini-pump for 11 days at a rate of 15 mg/kg/day. Chronic ISO infusion to C57BL mice caused concentric cardiac hypertrophy (sham; 4.1 +/- 0. 1, ISO; 5.2 +/- 0.2 mg/g heart to body weight ratio), accompanied by enhancement of cardiac collagen accurnulation, lipid peroxidation, superoxide generation and NADPH oxidase activity. The AT1a and beta-1,2 receptor mRNA expressions were down-regulated in the heart of ISO-infused mice. Olmesartan markedly suppressed cardiac mass enlargement as well as increases of oxidative indicators without any effects on heart rate. Olmesartan did not affect the cardiac angiotensin and beta-adrenergic receptor mRNA expression patterns. The AT1a receptor contribution to ISO-induced cardiac hypertrophy was reproduced in AT1aR(-/-) mice. These data suggest that the AT1 receptor plays a crucial role in the development of cardiac hypertrophy and oxidative stress under excessive beta-adrenergic stimulation, and that ARB treatment is beneficial for sympatho-excitatory cardiac hypertrophy and failure in mice. (c) 2007 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 59

リンク情報
DOI
https://doi.org/10.1016/j.yjmcc.2007.01.012
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000246287600013&DestApp=WOS_CPL