It has been reported that renovascular hypertension activates the renin-angiotensin system, leading to an increase in oxidative stress. We sought to determine whether renal-artery angioplasty improves endothelial dysfunction in patients with renovascular hypertension through a reduction in oxidative stress. We evaluated the response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after renal-artery angioplasty in 15 subjects with renovascular hypertension and 15 controls without hypertension who were matched for age and sex. Forearm blood flow was measured with the use of a mercury-filled Silastic strain-gauge plethysmograph. The forearm blood flow in response to acetylcholine was less in subjects with renovascular hypertension than in controls, although the forearm blood flow in response to isosorbide dinitrate was similar in the two groups. Angioplasty decreased systolic and diastolic blood pressures, forearm vascular resistance, and urinary excretion of 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein (LDL), indexes of oxidative stress. After angioplasty, the mean (+/-SD) forearm blood flow in response to acetylcholine was increased in the patients with renovascular hypertension (19.3+/-6.8 vs. 29.6+/-7.1 ml per minute per 100 ml, P=0.002). The increase in the maximal forearm blood flow in response to acetylcholine correlated significantly with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine (r=-0.51, P=0.004) and serum malondialdehyde-modified LDL (r=-0.39, P=0.02). Coinfusion of ascorbic acid (vitamin C) augmented the response of forearm blood flow to acetylcholine before angioplasty (P<0.001) but not after angioplasty. These findings suggest that excessive oxidative stress is involved, at least in part, in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.