VITAMIN-C IMPROVES ENDOTHELIUM-DEPENDENT VASODILATION IN FOREARM RESISTANCE VESSELS OF HUMANS WITH HYPERCHOLESTEROLEMIA

Background Endothelium-dependent vasodilation is impaired in humans wi th hypercholesterolemia. Oxidative degradation of endothelium-derived nitric oxide plays a major role in endothelial dysfunction in animal m odels of hypercholesterolemia. To assess whether this mechanism is rel evant to humans, we studied the effect of vitamin C, an antioxidant, o n vasodilator function in forearm resistance Vessels of patients with hypercholesterolemia. Methods and Results We studied 11 hypercholester olemic and 12 healthy control subjects. Forearm blood flow was determi ned by venous occlusion plethysmography. Endothelium-dependent vasodil ation was assessed by intra-arterial infusion of methacholine (0.3 to 10 mu g/min). Endothelium-independent vasodilation was measured by int ra-arterial infusion of nitroprusside (0.3 to 10 mu g/min) and verapam il (10 to 300 mu g/min). Forearm blood flow dose-response curves were determined for each drug before and during coadministration of Vitamin C (24 mg/min). In hypercholesterolemic subjects, endothelium-dependen t vasodilation to methacholine was augmented by coinfusion of vitamin C (P = .001); in contrast, endothelium-independent vasodilation to nit roprusside and verapamil were not affected by coinfusion of vitamin C (P = .8 and P = .3, respectively). In control subjects, vitamin C admi nistration did not alter endothelium-dependent vasodilation (P = .2). Conclusions We conclude that vitamin C improves endothelium-dependent vasodilation in the forearm resistance vessels of patients with hyperc holesterolemia. These findings suggest that nitric oxide degradation b y oxygen-derived free radicals contributes to abnormal vascular reacti vity in hypercholesterolemic humans.