INSULIN INCREASES VASCULAR SMOOTH-MUSCLE RECOVERY FROM INTRACELLULAR CALCIUM LOADS

Insulin has previously been shown to attenuate vasoconstrictor respons es to pressor agonists and accelerate vascular smooth muscle relaxatio n and vascular smooth muscle Ca2+ efflux. To further determine the rol e of insulin in regulating vascular smooth muscle Ca2+, quiescent A7r5 cultured vascular smooth muscle cells and human vascular smooth muscl e cells were incubated with or without 10(-7) or 10(-8) M insulin for 1 hour and then loaded with fura 2-AM; intracellular Ca2+ responses to and rates of recovery from angiotensin II (200 nM) and arginine vasop ressin (AVP) (10 muM) were studied fluorometrically in stirred suspens ion. Insulin (10(-7) M) caused an increase in the peak intracellular C a2+ response to angiotensin II (peak/baseline x 100 = 469+/-96 versus 288+/-74, P <.05) and a decrease in the peak Ca2+ response to vasopres sin (288+/-50 versus 389+/-33, P<.025). However, insulin also caused a marked increase in the rate of intracellular Ca2+ recovery to baselin e after stimulation with both angiotensin II (77.3+/-13.8 versus 30.6/-6 nM/min, P<.03) and vasopressin (P<.05), such that the cumulative e xposure to elevated intracellular Ca2+ after stimulation with either a gonist (ie, area under the intracellular Ca2+ curve) was reduced with insulin treatment. Insulin (10(-8)) caused small but still significant effects on all parameters in the A7r5 cells. Insulin also caused comp arable effects on Ca2+ recovery in the human cells hut was without sig nificant effect on peak Ca2+ responses to AVP. It is concluded that ac celerated removal of cytosolic Ca2+ after agonist stimulation is likel y to contribute to insulin attenuation of vasoconstrictor responses an d acceleration of vascular relaxation.