Insulin-stimulated vascular relaxation. Role of Ca(2+)-ATPase.
We have recently described defects in vascular smooth muscle Ca2+ transport in insulin-resistant states. Since insulin stimulates plasmalemmal Ca(2+)-ATPase activity in some tissues, loss of this stimulation in insulin resistance may result in reduced Ca2+ efflux, and, consequently, increased intracellular Ca2+ and vascular tone. Consequently, the present studies were conducted to determine the effects of insulin on vascular smooth muscle Ca2+ efflux and vascular relaxation following vasoconstriction, and to determine whether these effects are attributable to insulin stimulation of Ca(2+)-ATPase. Endothelium-denuded rat aortic strips were incubated for 1 h in the presence or absence of insulin (0.1 mU/mL), and 45Ca2+ efflux was measured. In some experiments, either a low Na+ (3 to 5 mmol/L) medium was used to inhibit Na+/Ca2+ exchange, vanadate (1 mmol/L) was added to inhibit Ca(2+)-ATPase activity, or the insulin level was varied (0.01 to 1.00 mU/mL) to establish dose dependence. To determine the effects of insulin on vascular relaxation, endothelial denuded aortic strips were suspended in a muscle bath and connected to an isometric force transducer. The strips were incubated with insulin (0.1 U/mL) or vehicle for 1 h, contracted with phenylephrine, and the rate of spontaneous relaxation following phenylephrine washout was measured. Insulin (0.1 mU/mL) stimulated both Ca2+ efflux (efflux rate constant = 0.288 +/- 0.038 v 0.361 +/- 0.036 min-1 in control and insulin-treated strips, respectively; P less than .005) and relaxation rate (3.97 +/- 0.35 v 4.63 +/- 0.31%/min; P less than .01), and both of these effects were inhibited by vanadate.(ABSTRACT TRUNCATED AT 250 WORDS)
Zemel
M B
MB
Department of Nutrition, University of Tennessee, Knoxville 37996-1900.
Johnson
B A
BA
Ambrozy
S A
SA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D007328:Insulin; D000252:Calcium-Transporting ATPases; D002118:Calcium