(Circulation. 2001;103:1618.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans
From the Cardiovascular Division (J.A.B., M.B.G., M.A.C.), Brigham and Women’s Hospital, and the Division of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School (A.B.G.), Boston, Mass.
Correspondence to Mark A. Creager, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail mcreager{at}rics.bwh.harvard.edu
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 µg/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 µg/min) without and with coadministration of NG-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.
Key Words: nitric oxide • diabetes mellitus • antioxidants • glucose
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