Modulation of oxidative stress by a selective inhibition of angiotensin II type 1 receptors in MI rats

OBJECTIVES To examine whether blocking of the renin-angiotensin system (RAS) at the angiotensin II type 1 (AT(1)) receptor site is accompanied by changes in the oxidative stress parameters. BACKGROUND Congestive heart failure in rats after myocardial infarction (MI) has been shown to correlate with a decrease in antioxidant enzyme activities and an increase in oxidative stress. Inhibition of the RAS with captopril improves cardiac function and survival in MI rats with a reduction in oxidative stress. METHODS Myocardial infarction in rats was produced by ligation of the left coronary artery. At four weeks after surgery, animals from the sham as well as MI groups were treated with losartan (2 mg/ml in drinking water daily). At 16 weeks after surgery, the animals were examined for hemodynamic function and the hearts were analyzed for antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and catalase) and oxidative stress (lipid hydroperoxides, reduced and oxidized glutathione and redox ratio). RESULTS Congestive heart failure was characterized dyspnea, depressed hemodynamic function and presence of lung and liver congestion. This was also associated with a decrease in the myocardial catalase (-25%), glutathione peroxidase (-38%) and superoxide dismutase (-42%) activities. An increase in oxidative stress in these hearts was indicated bq an increase in lipid hydroperoxides (+67%) and reduction ill the redox ratio (-75%). Hemodynamic function was better maintained and there were no indications of dyspnea or lung or liver congestion in the losartan-treated MI rats. In these animals, myocardial oxidative stress was markedly reduced and glutathione peroxidase and catalase activities were significantly improved compared with the untreated MI group. CONCLUSIONS Blocking of RAS at the AT(1) receptor site without the inhibition of angiotensin-converting enzymes modulates heart failure after MI, and this beneficial effect is associated with a decrease in oxidative stress. This study suggests a newer role for losartan in the treatment of heart failure. (J Am Coil Cardiol 2001;37:1461-6) (C) 2001 by the American College of Cardiology.