From the Cardiology Branch (C.C., C.M.K., R.O.C., J.A.P.) and the
Hypertension-Endocrine Branch (S.S.N., M.J.Q.), National Heart, Lung, and
Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Julio A. Panza, Cardiology Branch, National Institutes of Health, Bldg 10, Room 7B-15, Bethesda, MD 20892-1650. E-mail panzaj{at}gwgate.nhlbi.nih.gov
Abstract—Insulin-mediated
vasodilation has been proposed as an important determinant of
whole-body insulin-stimulated glucose disposal. However, it is not
clear whether the vasodilator effect of insulin results from a direct
action of the hormone or whether alternative mechanisms are involved.
To better characterize the mechanism of insulin-mediated
vasorelaxation, we compared forearm blood flow (FBF) responses to local
(intra-arterial) and systemic (intravenous,
euglycemic clamp) hyperinsulinemia in
10 healthy lean subjects using venous occlusion plethysmography. In
addition, we assessed the effect of nitric oxide (NO) synthase
inhibition by
NG-monomethyl-L-arginine
(L-NMMA) on the vasodilator and metabolic responses to
hyperinsulinemia. Similar forearm concentrations of
insulin were achieved during local and systemic infusion (231±39
versus 265±22 µU/mL; P=0.54). Of note, FBF did not
change significantly in response to local
hyperinsulinemia (from 2.6±0.3 to 2.4±0.3 mL
· min-1 · dL-1;
P=0.50). In contrast, systemic
hyperinsulinemia caused a 52% increase in FBF
(from 2.5±0.2 to 3.8±0.5 mL · min-1 ·
dL-1; P<0.004), which was reversed by
L-NMMA (FBF decreased from 3.8±0.5 to 2.3±0.2 mL ·
min-1 · dL-1; P=0.004).
We conclude that systemic, but not local,
hyperinsulinemia induces vasodilation in the
forearm. Our findings suggest that insulin-mediated vasodilation is not
due solely to a direct stimulatory effect of insulin but involves
additional mechanisms activated only during systemic
hyperinsulinemia.
© 1998 American Heart Association, Inc.
Scientific Contributions
Vasodilator Response to Systemic But Not to Local Hyperinsulinemia in the Human Forearm
Key Words: insulin • vasodilation • glucose • nitric oxide • L-NMMA
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