Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo

Stephen B. Williams, Allison B. Goldfine, Farris K. Timimi, Henry H. Ting, Mary Anne Roddy, Donald C. Simonson, Mark A. Creager

Research output: Contribution to journalArticlepeer-review

646 Scopus citations


Background - Endothelial function is impaired in patients with diabetes mellitus. However, the factors contributing to this defect are currently unknown. Hyperglycemia attenuates endothelium-dependent relaxation in normal rabbit arteries in vitro and rat arterioles in vivo. Accordingly, this study examined the effect of acute hyperglycemia on endothelium-dependent vasodilation in nondiabetic humans in vivo. Methods and Results - Endothelium-dependent vasodilation was assessed through brachial artery infusion of methacholine chloride both before and during 6 hours of local hyperglycemia (300 mg/dL) achieved by intra-arterial infusion of 50% dextrose. Forearm blood flow was determined by plethysmography. In a group of 10 subjects, there was a trend toward attenuated methacholine-mediated vasodilation during hyperglycemia compared with euglycemia (P=.07 by ANOVA; maximal response, 13.3±2.8 versus 14.7±1.5 mL · min-1 · 100 mL-1, respectively). In these subjects, the systemic serum insulin levels increased significantly during the dextrose infusion (P<.001). To eliminate the confounding vasoactive effects of insulin, the protocol was repeated during systemic infusion of octreotide (30 ng · kg-2 · min-1) to inhibit pancreatic secretion of insulin. In these subjects (n = 10), hyperglycemia significantly attenuated the forearm blood flow response to methacholine (P<.01 by ANOVA; maximal response, 16.9±2.5 before versus 12.7±1.8 mL · min-1 · 100 mL-1 during hyperglycemia). Methacholine-mediated vasodilation was not attenuated by an equimolar infusion of mannitol (P>.40), nor did hyperglycemia reduce endothelium-independent vasodilation to verapamil (P>.50). Conclusions - Acute hyperglycemia impairs endothelium- dependent vasodilation in healthy humans in vivo. This finding suggests that elevated glucose may contribute to the endothelial dysfunction observed in patients with diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)1695-1701
Number of pages7
Issue number17
StatePublished - May 5 1998


  • Diabetes mellitus
  • Endothelium-derived factors
  • Glucose
  • Nitric oxide
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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