INSULIN REDUCES CONTRACTION AND INTRACELLULAR CALCIUM-CONCENTRATION IN VASCULAR SMOOTH-MUSCLE

Resistance to insulin-induced glucose disposal is associated with hype rtension, in accord with recent reports that insulin-induced vasodilat ion is impaired in men with resistance to insulin-induced glucose disp osal. Nevertheless, the mechanism of insulin-induced vasodilation is n ot known. We wished to determine whether a physiological concentration of insulin inhibits agonist-induced contraction at the level of the i ndividual vascular smooth muscle cell, and if so, how. Dispersed vascu lar smooth muscle cells from dog femoral artery were grown on collagen gels for 4 to 8 days. Contraction and intracellular Ca2+ concentratio n of individual cells were measured by photomicroscopy and fura 2 epif luorescence microscopy, respectively. Serotonin and angiotensin II con tracted cells in a dose-dependent manner. Preincubation of cells for 2 0 minutes (short-term) or 7 days (long-term) with insulin (40 muU/mL) inhibited serotonin- and angiotensin II-induced contractions by approx imately 50%. Insulin (10 muU/mL) acutely inhibited serotonin-induced c ontraction by 34%. The maximal effect of high extracellular K+-induced contraction was not affected by short-term insulin exposure, but the ED50 for extracellular K+-induced contraction was increased from 7.6+/ -2.5 to 16.0+/-3.9 mmol/L (P<.05). Short-term insulin exposure also at tenuated the peak rise of the serotonin-induced intracellular Ca2+ tra nsient and increased the rate constant for intracellular Ca2+ decline. Verapamil and ouabain completely blocked the attenuation of agonist-i nduced contraction by short-term insulin exposure, indicating the impo rtance of voltage-operated Ca2+ channels and the Na+-K+ pump for this effect. We conclude that a physiological insulin concentration inhibit s extracellular K+- and agonist-induced contractions at the level of t he vascular smooth muscle cell and attenuates the intracellular Ca2+ t ransient in agonist-stimulated cells. Insulin may stimulate Na+-K+ pum p activity, which hyperpolarizes the cell, thereby decreasing Ca2+ inf lux via voltage-operated channels.