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 Ca ²⁺ 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 μM; inhibitor of protein synthesis) nor tamoxifen (1 μM; blocker of estrogenic receptors) modified the effects of estradiol. Estradiol (100 μM) also blocked the contractile response to serotonin (10 μM) but not to caffeine (10 mM). In addition, estradiol (100 μM) inhibited the contractile responses to cyclopiazonic acid (1 μM; selective Ca²⁺-ATPase inhibitor) associated with capacitative Ca ²⁺ 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 Ca ²⁺-dependent contractile effects mediated by the stimuli of α₁-adrenergic and serotonergic receptors and inhibited the capacitative Ca²⁺ influx through both L-type and non-L-type Ca ²⁺ channels. Such effects are in essence nongenomic and not mediated by the intracellular estrogenic receptor.