Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice
Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice
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DOI：
10.1016/j.yjmcc.2007.01.012
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发表时间：
2007-04-01
影响因子：
5
通讯作者：
Kimura, Shoji
中科院分区：
文献类型：
--
作者：
Zhang, Guo-Xing;Ohmori, Koji;Kimura, Shoji
交感神经和肾素-血管紧张素系统活动升高是心力衰竭的共同特征。本研究旨在研究AT1受体拮抗剂（ARB）和AT1a受体缺陷（AT1aR(-/-)）小鼠在过度β -肾上腺素受体刺激时，AT1受体在心脏肥厚和氧化应激中的作用。以15mg /kg/天的剂量给药于经ARB（奥美沙坦）治疗或不经ARB（奥美沙坦）治疗的C57BL小鼠和经渗透微型泵皮下植入的AT1aR（-/-）小鼠，持续11天。慢性ISO输注C57BL小鼠引起同心性心肌肥厚(sham; 4.1 +/- 0。1、ISO;5.2 +/- 0.2 mg/g心重比)，同时心脏胶原积累、脂质过氧化、超氧化物生成和NADPH氧化酶活性增强。在iso灌注小鼠心脏中，AT1a和β 1,2受体mRNA表达下调。奥美沙坦明显抑制心脏肿块增大和氧化指标的增加，而对心率没有任何影响。奥美沙坦不影响心脏血管紧张素和β -肾上腺素能受体mRNA的表达模式。在AT1aR（-/-）小鼠中重现了AT1a受体对iso诱导的心肌肥厚的贡献。这些数据表明，在过度的β -肾上腺素能刺激下，AT1受体在心脏肥大和氧化应激的发展中起着至关重要的作用，并且ARB治疗有益于小鼠交感神经兴奋性心脏肥大和心力衰竭。(c) 2007爱思唯尔公司版权所有。
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.