Insulin Reduces Contraction and Intracellular Calcium Concentration in Vascular Smooth Muscle

Resistance to insulin-induced glucose disposal is associated with hypertension, in accord with recent reports that insulin-induced vasodilation is impaired in men with resistance to insulin-induced glucose disposal. Nevertheless, the mechanism of insulin-induced vasodilation is not known. We wished to determine whether a physiological concentration of insulin inhibits agonist-induced contraction at the level of the individual vascular smooth muscle cell, and if so, how. Dispersed vascular smooth muscle cells from dog femoral artery were grown on collagen gels for 4 to 8 days. Contraction and intracellular Ca concentration of individual cells were measured by photomicroscopy and fura 2 epifluorescence microscopy, respectively. Serotonin and angiotensin II contracted cells in a dose-dependent manner. Preincubation of cells for 20 minutes (short-term) or 7 days (long-term) with insulin (40 μU/mL) inhibited serotonin- and angiotensin II–induced contractions by approximately 50%. Insulin (10 μU/mL) acutely inhibited serotonin-induced contraction 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