Insulin inhibits dog vascular smooth muscle contraction and lowers Ca2+i by inhibiting Ca2+ influx.
Essential hypertension, obesity and non-insulin-dependent diabetes are associated with resistance to insulin-induced glucose disposal. Because physiological concentrations of insulin inhibit vascular smooth muscle (VSM) contraction in vivo, it has been proposed that resistance to insulin-induced inhibition of VSM contraction might be partly responsible for the elevated vascular resistance found in these clinical conditions. Nevertheless, it is not known how insulin inhibits contraction of normal VSM. Several workers have demonstrated that insulin attenuates the agonist-induced intracellular Ca2+ (Ca2+i) transient in VSM, although the identity of the sarcolemmal and/or sarcoplasmic reticular Ca2+ transport systems that are affected by insulin is controversial. Our laboratory has examined the effects of a physiological concentration of insulin on contraction and Ca2+ transport in cultured VSM cells from canine femoral artery. We have found that insulin inhibits agonist-induced contraction and attenuates the agonist-induced Ca2+i transient by inhibiting Ca2+ influx, but not by increasing Ca2+ efflux or inhibiting Ca2+ release from internal stores. Insulin also stimulates ouabain-sensitive 86Rb+ uptake (Na(+)-K+ pump activity) and does not inhibit VSM contraction in the presence of ouabain. Our data support the hypothesis that insulin stimulates Na(+)-K+ pump activity, resulting in hyperpolarization of the cell and decreased Ca2+ influx via voltage-operated channels.
Kahn
A M
AM
University of Texas Medical School, Houston 77030, USA.
Song
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology
D007328:Insulin; D012701:Serotonin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium