Endothelium-dependent effects of estrogen on vasomotor tone: Consequences of nongenomic actions

Clinical observational and experimental studies indicate that estrogen has acute and prolonged effects on vascular function. Acute effects not requiring gene transcription or nongenomic responses include changes in intracellular calcium and activation of second messenger systems including release of endothelium-derived nitric oxide. However, interactions between rapid effects of estrogen and modulation of subsequent responses of endothelial cells are lacking. Experiments were designed to determine effects of estrogen on subsequent responses of endothelial cells to vasoactive stimuli. Human umbilical vein endothelial cells were cultured on coverslips and changes in intracellular calcium concentrations measured to 17β-estradiol and histamine. Estradiol alone did not increase intracellular calcium or modulate the peak calcium response to histamine. However, the decay of the peak calcium response to histamine was more rapid in the presence, compared to the absence, of estradiol. These results provide proof of principal that estradiol modulates responses of endothelial cells to vasoactive stimuli through changes in regulation of intracellular calcium.