VITAMIN-C IMPROVES ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus, Inactivation of endothelium-derived nitric oxide by oxygen- derived free radicals contributes to abnormal vascular reactivity in e xperimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes me llitus, We studied 10 diabetic subjects and 10 age-matched, nondiabeti c control subjects, Forearm blood flow was determined by venous occlus ion plethysmography. Endothelium-dependent vasodilation was assessed b y intraarterial infusion of methacholine (0.3-10 mu g/min). Endotheliu m-independent vasodilation was measured by intraarterial infusion of n itroprusside (0.3-10 mu g/min) and verapamil (10-300 mu g/min). Forear m blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min, In diabetic subjects, endothelium-dependent vasodilation to me thacholine was augmented by simultaneous infusion of vitamin C (P = 0. 002); in contrast, endothelium-independent vasodilation to nitroprussi de and to verapamil were not affected by concomitant infusion of vitam in C (P = 0.9 and P = 0.4, respectively), In nondiabetic subjects, vit amin C administration did not alter endothelium-dependent vasodilation (P = 0.8). The conclude that endothelial dysfunction in forearm resis tance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C, Thes e findings support the hypothesis that nitric oxide inactivation by ox ygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.