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(Hypertension. 1997;30:928-933.)
© 1997 American Heart Association, Inc.

Articles

Insulin Acutely Inhibits Cultured Vascular Smooth Muscle Cell Contraction by a Nitric Oxide Synthase–Dependent Pathway

Andrew M. Kahn; Annat Husid; Julius C. Allen; Charles L. Seidel; ; Tom Song

From the Departments of Medicine, The University of Texas Health Science Center, Houston (A.M.K., A.H., T.S.), and Baylor College of Medicine (J.C.A.), Houston, Tex.

Correspondence to Andrew M. Kahn, MD, 4.138 MSB, University of Texas Health Science Center, PO Box 20708, Houston, TX 77225.

Abstract Insulin acutely decreases contractile agonist-induced Ca²⁺ influx and contraction in endothelium-free cultured vascular smooth muscle (VSM) cells, but the mechanism is not known. Since it has been reported that insulin-induced vasodilation in humans is linked to nitric oxide synthase activity, we wished to determine whether insulin inhibits Ca²⁺ influx and contraction of cultured vascular smooth muscle cells by a nitric oxide synthase–dependent pathway. Primary cultures of endothelial cell–free VSM cells from canine femoral artery were preincubated with and without 1 nmol/L insulin for 30 minutes, and the 5-minute production of cGMP was measured. Insulin alone did not affect cGMP production, but in the presence of 10^-5 mol/L serotonin insulin stimulated cGMP production by 60%. N^G-monomethyl-L-arginine (0.1 mmol/L), an inhibitor of nitric oxide synthase, inhibited the conversion of arginine to citrulline by these cells, blocked insulin-stimulated cGMP production, and blocked the inhibition by insulin of 5-hydroxytryptamine (5-HT)–stimulated Mn⁺² (a Ca²⁺ surrogate) influx and contraction. Insulin did not affect contraction of VSM cells grown under conditions designed to deplete the cells of tetrahydrobiopterin, an essential cofactor of nitric oxide synthase. These studies demonstrate that insulin acutely inhibits 5-HT–stimulated Ca²⁺ influx and contraction of endothelium-free cultured VSM cells by a nitric oxide synthase–dependent mechanism.

Key Words: serotonin • cyclic GMP • fura-2 • Ca²⁺ transport • arginine

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