INSULIN INHIBITS DOG VASCULAR SMOOTH-MUSCLE CONTRACTION AND LOWERS CA2+(I) BY INHIBITING CA2+ INFLUX

Essential hypertension, obesity and noninsulin-dependent diabetes are associated with resistance to insulin-induced glucose disposal. Becaus e physiological concentrations of insulin inhibit vascular smooth musc le (VSM) contraction in vivo, it has been proposed that resistance to insulin-induced inhibition of VSM contraction might be partly responsi ble for the elevated vascular resistance found in these clinical condi tions. Nevertheless, it is not known how insulin inhibits contraction of normal VSM. Several workers have demonstrated that insulin attenuat es the agonist-induced intracellular Ca2+ (Ca-i(2+)) transient in VSM, although the identity of the sarcolemmal and/or sarcoplasmic reticula r Ca2+ transport systems that are affected by insulin is controversial . Our laboratory has examined the effects of a physiological concentra tion of insulin on contraction and Ca2+ transport in cultured VSM cell s from canine femoral artery. We have found that insulin inhibits agon ist-induced contraction and attenuates the agonist-induced Ca-i(2+) tr ansient by inhibiting Ca2+ influx, but not by increasing Ca2+ efflux o r inhibiting Ca2+ release from internal stores. Insulin also stimulate s ouabain-sensitive Rb-86(+) uptake (Na+-K+ pump activity) and does no t inhibit VSM contraction in the presence of ouabain. Our data support the hypothesis that insulin stimulates Na+-K+ pump activity, resultin g in hyperpolarization of the cell and decreased Ca2+ influx via volta ge-operated channels.