INHIBITORY EFFECTS OF INSULIN ON CYTOSOLIC CA2+ LEVEL AND CONTRACTION IN THE RAT AORTA - ENDOTHELIUM-DEPENDENT AND ENDOTHELIUM-INDEPENDENT MECHANISMS

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 NG-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).