| First Author | Zhang GX | Year | 2007 |
| Journal | J Mol Cell Cardiol | Volume | 42 |
| Issue | 4 | Pages | 804-11 |
| PubMed ID | 17350036 | Mgi Jnum | J:120810 |
| Mgi Id | MGI:3708037 | Doi | 10.1016/j.yjmcc.2007.01.012 |
| Citation | Zhang GX, et al. (2007) Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice. J Mol Cell Cardiol 42(4):804-11 |
| abstractText | 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 accumulation, 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. |
