Endothelium-dependent hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor(EDHF) diminish with aging as well as by hypertension. Antihypertensive treatment improved the endothelial dysfunction associated with hypertension. We here tested whether the angiotensin II receptor antagonist candesartan or the converting enzyme inhibitor enalapril would improve the age-related impairment of the EDHF-mediated responses in normotensive rats. EDHF-mediated hyperpolarization and relaxation to acetylcholine in mesenteric arteries were improved similarly in both candesartan- and enalapril-treated aged rats, but not in rats treated with the traditional combination of hydralazine and hydrochlorothiazide. These findings suggest that the inhibitors of renin-angiotensin system might serve as novel tools to prevent the endothelial dysfunction associated with aging.