From the Vascular Medicine and Atherosclerosis Unit of the Cardiovascular
Division, Brigham and Women's Hospital (S.B.W., F.K.T., H.H.T., M.-A.
R., M.A.C.) and the Endocrine Division of the Brigham and Women's
Hospital and the Joslin Diabetes Center (A.B.G., D.C.S.), Harvard Medical
School, Boston, Mass.
Correspondence to Mark A. Creager, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail macreager{at}bics.bwh.harvard.edu
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-1 · 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.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Acute Hyperglycemia Attenuates Endothelium-Dependent Vasodilation in Humans In Vivo
Key Words: diabetes mellitus • endothelium-derived factors • vasodilation • glucose • nitric oxide
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