Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans

Background-Endothelium-dependent vasodilation is impaired in patients with insulin-dependent and non-insulin-dependent diabetes mellitus and restored by vitamin C administration, implicating a causative role for oxidant stres s. Hyperglycemia per se attenuates endothelium-dependent vasodilation;in he althy subjects. Accordingly, this study investigated whether impaired endot helium-dependent vasodilation caused by hyperglycemia in nondiabetic humans is restored by administration of the antioxidant vitamin C. Methods and Results-Endothelium-dependent vasodilation was measured by incr emental brachial artery administration of methacholine chloride (0.3 to 10 mug/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) crea ted by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodila tion was significantly diminished by hyperglycemia (P=0.02 by ANOVA) and re stored by vitamin C (P=0.04). In contrast, endothelium-dependent vasodilati on was not affected by equimolar infusions of mannitol, with and without vi tamin C coinfusion (P NS). Endothelium-independent vasodilation was measure d by incremental infusion of verapamil chloride (10 to 300 mug/min) without and with coadministration of N-G-monomerhyl-L-arginine (L-NMMA). In the ab sence of L-NMMA, endothelium-independent vasodilation was not significantly altered during hyperglycemia (P=NS) but was augmented by vitamin C (P=0.04 ). The coadministration of L-NMMA eliminated the vitamin C-related augmenta tion in verapamil-mediated vasodilation. Conclusions-Vitamin C administration restores endothelium-dependent vasodil ation impaired by acute hyperglycemia in healthy humans in vivo. These find ings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.