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(Circulation Research. 1995;77:673-678.)
© 1995 American Heart Association, Inc.

Articles

Inhibitory Effects of Insulin on Cytosolic Ca²⁺ Level and Contraction in the Rat Aorta

Endothelium-Dependent and -Independent Mechanisms

Shu-Zhong Han, Yasuyoshi Ouchi, Hideaki Karaki, Hajime Orimo

From the Department of Geriatrics, Faculty of Medicine (S.-Z.H., Y.O., H.O.), and the Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences (H.K.), The University of Tokyo (Japan).

Correspondence to Yasuyoshi Ouchi, MD, PhD, Department of Geriatrics, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan.

Abstract To determine the mechanism of the inhibitory effect of insulin on vascular tone, contraction was measured simultaneously with endothelial and smooth muscle cytosolic Ca²⁺ level ([Ca²⁺]_i) in the isolated rat aorta. Insulin (200 mU/mL) increased endothelial [Ca²⁺]_i and decreased resting muscle tone. The removal of endothelium abolished the effects of insulin. In the aorta precontracted with norepinephrine, insulin (3 to 120 mU/mL) induced concentration-dependent inhibition of contraction. The relaxant effect followed the increase in endothelial [Ca²⁺]_i and decrease in smooth muscle [Ca²⁺]_i. The relaxant effect was attenuated by removal of endothelium or by the addition of 10^-5 mol/L N^G-monomethyl-L-arginine but not by 10^-5 mol/L indomethacin. In the absence of endothelium, the relaxant effect of insulin followed the decrease in smooth muscle [Ca²⁺]_i. These results suggest that insulin inhibits vascular contraction by dual mechanisms in the isolated rat aorta: (1) Insulin acts on vascular endothelium by increasing endothelial [Ca²⁺]_i and releasing NO, which decreases smooth muscle [Ca²⁺]_i and the Ca²⁺ sensitivity of the contractile elements. (2) Insulin also directly acts on smooth muscle and decreases smooth muscle [Ca²⁺]_i.

Key Words: insulin • cytosolic Ca²⁺ • endothelium-derived relaxing factor • rat aortic smooth muscle • rat aortic endothelium

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