Vitamin C improves attenuated angiotensin II-induced endothelium-dependent vasodilation in human forearm vessels.

Endothelial dysfunction might be related to an increase in superoxide anion production in patients with hypertension, hypercholesterolemia, diabetes mellitus, and heart failure. Studies in animal models indicate that angiotensin II increases superoxide anion production by vascular tissues. We examined whether angiotensin II attenuates endothelium-dependent vasodilation via an increase in superoxide anion production in human forearm vessels in vivo. Forearm blood flow was measured in 23 healthy young men. We examined forearm vasodilator responses to an intra-arterial infusion of acetylcholine (4, 8, and 16 microg/min) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min) before and during an intra-arterial infusion of anglotensin II (n=8), angiotensin II plus vitamin C (n=8), and vitamin C alone (n=4). Angiotensin II attenuated the forearm vasodilatory response to acetylcholine (p<0.05), and this attenuated response was abolished by vitamin C. Angiotensin II did not alter the forearm vasodilatory response to sodium nitroprusside, and vitamin C infusion did not affect the forearm vasodilatory response to either acetylcholine or sodium nitroprusside. The forearm vasodilator response to acetylcholine did not change during infusion of norepinephrine (n=3), which reduced forearm blood flow to a degree similar to that by angiotensin II infusion. These results suggest that angiotensin II attenuates endothelium-dependent forearm vasodilation, and vitamin C improves this impairment. Thus, angiotensin II likely attenuates endothelium-dependent vasodilation via an increase of superoxide anion production in the human forearm in vivo.