Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 4th communication: improvement of heart failure of rats with myocardial infarction by valasartan.

The hemodynamic effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)bipheneoyl-4-yl]meth yl¿valine, CAS 137862-53-4, CGP 48933), a new angiotensin II type 1 receptor antagonist, on rats with myocardial infarction induced by coronary artery ligation was examined. Four weeks after ligation, mean blood pressure, left ventricular pressure and cardiac output decreased, while left ventricular end-diastolic pressure increased in control rats. Left ventricular end-diastolic pressure significantly decreased in rats treated with valsartan at 30 mg/kg/d p.o. for 4 weeks. Total systemic resistance remarkably decreased in those with enalapril 3 mg/kg/d p.o. and valsartan 30 mg/kg/d p.o. Valsartan and enalaprilat did not affect cardiac functions of isolated intact rat hearts before and after ischemia in Langendorff apparatus. In addition to hemodynamic effects observed in vivo, valsartan at 30 mg/kg p.o. significantly inhibited left ventricular hypertrophy. Valsartan would thus appear to be clinically useful for treating heart failure following myocardial infarction.