Insulin significantly stimulated Ca2+ efflux (0.361 vs 0.288 min^-1; P<0.005) and relaxation rate (4.63 vs 3.97 %/min; P<0.01) in rat aortic strips, likely via Ca2+-ATPase stimulation.
Does insulin improve vascular relaxation and Ca2+ efflux in endothelium-denuded rat aortic strips?
Insulin stimulates vascular smooth muscle Ca2+ efflux and vascular relaxation, likely via stimulation of Ca2+-ATPase, suggesting a mechanism for increased vascular resistance in insulin-resistant states.
Absolute Event Rate: 0.361% vs 0.288%
p-value: p=<.005
We have recently described defects in vascular smooth muscle Ca2+ transport in insulin-resistant states. Since insulin stimulates plasmalemmal Ca2+- 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 Ca2+- ATPase. Endothelium-denuded rat aortic strips were incubated for 1 h in the presence or absence of insulin (0.1 mU/mL), and 4 5Ca2+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 Ca2+-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 υ 0.361 ± 0.036 min"1 in control and insulin-treated strips, respectively; P < .005) and relaxation rate (3.97 ± 0.35 υ 4.63 ± 0.31%/min; P < .01), and both of these effects were inhibited by vanadate. In contrast, inhibition of Na+ / Ca2+ exchange reduced Ca2+ efflux, but the effect of insulin was maintained. Insulin stimulation of Ca2+ efflux exhibited dose dependence over the range of concentrations tested. These results indicate that insulin stimulates vascular smooth muscle Ca2+ efflux and vascular relaxation and that both effects appear to be due to stimulation of Ca2+-ATPase. We propose that the increased vascular resistance characteristics of insulin resistance may result, in part, from vascular smooth muscle resistance to these effects of insulin. Am J Hypertens 1992;5:637-641.
Zemel et al. (1992) studied Vascular tone / Insulin resistance. Insulin vs. Vehicle/control was evaluated on Ca2+ efflux rate constant (min^-1) (p=<.005). Insulin significantly stimulated Ca2+ efflux (0.361 vs 0.288 min^-1; P<0.005) and relaxation rate (4.63 vs 3.97 %/min; P<0.01) in rat aortic strips, likely via Ca2+-ATPase stimulation.