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

Joshua A. Beckman, Allison B. Goldfine, Mary Beth Gordon, Mark A. Creager

Research output: Contribution to journalArticlepeer-review

275 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1618-1623
Number of pages6
Issue number12
StatePublished - Mar 27 2001
Externally publishedYes


  • Antioxidants
  • Diabetes mellitus
  • Glucose
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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