Inhibitory Effects of Insulin on Cytosolic Ca 2+ Level and Contraction in the Rat Aorta

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Abstract
To determine the mechanism of the inhibitory effect of insulin on vascular tone, contraction was measured simultaneously with endothelial and smooth muscle cytosolic Ca 2+ level ([Ca 2+ ] i ) in the isolated rat aorta. Insulin (200 mU/mL) increased endothelial [Ca 2+ ] 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 [Ca 2+ ] i and decrease in smooth muscle [Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] i and releasing NO, which decreases smooth muscle [Ca 2+ ] i and the Ca 2+ sensitivity of the contractile elements. (2) Insulin also directly acts on smooth muscle and decreases smooth muscle [Ca 2+ ] i .