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  • Title: Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans.
    Author: Beckman JA, Goldfine AB, Gordon MB, Creager MA.
    Journal: Circulation; 2001 Mar 27; 103(12):1618-23. PubMed ID: 11273987.
    Abstract:
    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 stress. Hyperglycemia per se attenuates endothelium-dependent vasodilation in healthy subjects. Accordingly, this study investigated whether impaired endothelium-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 incremental brachial artery administration of methacholine chloride (0.3 to 10 microg/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) created by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodilation was significantly diminished by hyperglycemia (P:=0.02 by ANOVA) and restored by vitamin C (P:=0.04). In contrast, endothelium-dependent vasodilation was not affected by equimolar infusions of mannitol, with and without vitamin C coinfusion (P:=NS). Endothelium-independent vasodilation was measured by incremental infusion of verapamil chloride (10 to 300 microg/min) without and with coadministration of N:(G)-monomethyl-L-arginine (L-NMMA). In the absence 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 augmentation in verapamil-mediated vasodilation. CONCLUSIONS: Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.
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