Issue Archive

Simvastatin inhibits hypertension--induced cardiac hypertrophy in rats through activation of heme oxygenase--1/carbon monoxide pathway

Yao Haimu, Wu Xuesi, Zhang Jing, Geng Bin, Tang Chaoshu

Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Science.Beijing 100029；China

Abstract

To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight male Wistar rats were randomly allocated to four groups. Rats in model group received nitric oxide synthase inhibitor, N-nitro-L-arginine （L-NNA） 15 mg/（kg·d） by peritoneal injection. Rats in simvastatin treatment groups were given simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/ （kg·d） intragastrically respectively. Rats in control group received the same volume of normal sodium. Left ventricular function, left ventricular mass index （LVMI）, the content of brain natriuretic peptide （BNP） in plasma and myocardium, myocardial hydroxyproline and heme oxygenase activity were determined after 6 weeks. The results showed that rats in model group developed significant cardiac hypertrophy associated with reduced left ventricular function compared with the control group. However, compared with the model group, L-NNA-induced cardiac hypertrophy of rats was significantly relieved in simvastatin treatment groups, associated with improved left ventricular function, decreased LVMI, lower BNP levels in plasma and myocardium, lower content of myocardial hydroxyproline, and increased myocardial heme oxygenase （HO） activity. In cultured rat neonatal cardiomyocytes, simvastatin （30 or 100μmol/L） significantly increased heme oxygenase-1 （HO-1） mRNA expression, HO activity as well as the production of CO in cardiomyocytes. Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not change [~(3)H]leucine uptake of cardiomyocytes. However, cocultured with simvastatin significantly inhibited the cardiomyocyte [3H]leucine uptake induced by angiotensin Ⅱ in a concentration- dependent manner. Cotreatment with zinc protoporphyrin significantly abolished the suppressive effect of simvastatin on cardiomyocyte [^3H]leucine uptake. These data suggest that the activation of HO-1/CO pathway may be one of the important mechanisms by which statins inhibit cardiac hypertrophy caused by hypertension.

Key words: simvastatin;Cardiac hypertrophy;heme oxygenase

Received: 　　Accepted:

Corresponding author: 　　E-mail:

Citing This Article：

Yao Haimu, Wu Xuesi, Zhang Jing, Geng Bin, Tang Chaoshu. Simvastatin inhibits hypertension--induced cardiac hypertrophy in rats through activation of heme oxygenase--1/carbon monoxide pathway. Acta Physiol Sin 2006; 58 (2): (in Chinese with English abstract).