ACUTE HYPERGLYCEMIA ATTENUATES ENDOTHELIUM-DEPENDENT VASODILATION IN HUMANS IN-VIVO

Background-Endothelial function is impaired in patients with diabetes mellitus, However, the factors contributing to this defect are current ly unknown. Hyperglycemia attenuates endothelium-dependent relaxation in normal rabbit arteries in vitro and rat arterioles in vivo. Accordi ngly, this study examined the effect of acute hyperglycemia on endothe lium-dependent vasodilation in nondiabetic humans in vivo. Methods and Results-Endothelium-dependent vasodilation was assessed through brach ial artery infusion of methacholine chloride both before and during 6 hours of local hyperglycemia (300 mg/dL) achieved by intra-arterial in fusion of 50% dextrose, Forearm blood flow was determined by plethysmo graphy, 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 dextr ose infusion (P<.001), To eliminate the confounding vasoactive effects of insulin, the protocol was repeated during systemic infusion of oct reotide (30 ng . kg(-1). min(-1)) to inhibit pancreatic secretion of i nsulin. In these subjects (n=10), hyperglycemia significantly attenuat ed the forearm blood flow response to methacholine (P<.01 by ANOVA; ma ximal response, 16.9+/-2.5 before versus 12.7+/-1.8 mL . min(-1). 100 mL(-1) during hyperglycemia). Methacholine-mediated vasodilation was n ot attenuated by an equimolar infusion of mannitol (P>.40), nor did hy perglycemia reduce endothelium-independent vasodilation to verapamil ( P>.50), Conclusions-Acute hyperglycemia impairs endothelium-dependent vasodilation in healthy humans in vivo. This finding suggests that ele vated glucose may contribute to the endothelial dysfunction observed i n patients with diabetes mellitus.