Effects of estradiol on phenylephrine contractility associated with intracellular calcium release in rat aorta

The ability of estradiol to affect phenylephrine-induced contraction and the subsequent increase in resting tone, associated with capacitative Ca2+ entry across the plasma membrane, was evaluated in rat aortic rings incubated in Ca2+-free solution. The incubation with estradiol (1 - 100 nM, 5 min) inhibited both the phenylephrine-induced contraction and the IRT. Neither cycloheximide (1 mu M; inhibitor of protein synthesis) nor tamoxifen (1 mu M; blocker of estrogenic receptors) modified the effects of estradiol. Estradiol ( 100 mu M) also blocked the contractile response to serotonin ( 10 mu M) but not to caffeine ( 10 mM). In addition, estradiol ( 100 mu M) inhibited the contractile responses to cyclopiazonic acid ( 1 mu M; selective Ca2+-ATPase inhibitor) associated with capacitative Ca2+ influx through non-L-type Ca2+ channels. Finally, estradiol inhibited the Ca2+-induced increases in intracellular free Ca2+ ( after pretreatment with phenylephrine) in cultured rat aorta smooth muscle cells incubated in Ca2+-free solution. In conclusion, estradiol interfered in a concentration-dependent manner with Ca2+-dependent contractile effects mediated by the stimuli of alpha(1)-adrenergic and serotonergic receptors and inhibited the capacitative Ca2+ influx through both L-type and non-L- type Ca2+ channels. Such effects are in essence nongenomic and not mediated by the intracellular estrogenic receptor.