Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 2nd communication: valsartan prevents end-organ damage in spontaneously hypertensive stroke-prone rats during 1-year treatment.

Valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl¿ valine, CAS 137862-53-4, CGP 48933), a non-peptide angiotensin II type 1 receptor antagonist, or enalapril was administered to spontaneously hypertensive rats stroke-prone (SHR-SP) for 1 year from 8 weeks to 56 weeks of age under a normal diet without saline load. During 48 weeks, control rats showed increase in systolic blood pressure from 180 to 250 mmHg accompanying stroke-related behaviour, cardiac and aortic hypertrophy, hyperreactive contractility of mesenteric vascular beds, proteinuria, high water turnover and death. Valsartan at 3, 10 and 30 mg/kg/d p.o. and enalapril at 1 and 10 mg/kg/d p.o suppressed the increase in blood pressure dose-dependently. Systolic blood pressure was steadily controlled to around 180 mmHg at the highest dose of either drug throughout the study. In proportion to the antihypertensive action of the drugs, end-organ damage was prevented. During 1-year administration, effects of enalapril and valsartan were much the same, indicating the clinical usefulness of valsartan being comparable to enalapril.