Estrogen Induces Coronary Arterial Dilation via Downregulation of Voltage‐gated, Ca2+ Channels

Abstract

Gender studies have suggested that the female sex protects against abnormal vascular tone. Our lab has previously shown that estrogen (E2) can downregulate voltage‐gated, L‐type Ca2+ channels (VGCCs) to prevent excessive vasoconstriction. The aim of this study is to determine the mechanisms associated with this E2‐induced downregulation. The right coronary artery was obtained from hearts of female pigs. Coronary arteries were sectioned into longitudinal strips (Western blots, Real‐time PCR) or rings (isometric tension) and cultured for 24 hrs in 1nM E2 or EtOH (E2 solvent). The role of the endothelium was evaluated by removing the endothelium of the artery with a toothpick before the 24 hr incubation period. E2 decreased the protein expression of the pore‐forming α1C subunit of the VGCC by 35%, but did not affect the mRNA encoding the α1C subunit. This decrease was not affected by the presence of the endothelium. Isometric contractions were also measured to the VGCC agonist, FPL64176, in endothelial intact and denuded rings. Although E2 decreased the FPL64176 contraction by 50%, the presence of the endothelium had no effect. To determine the role of estrogen receptors (ER) the arterial strips were incubated with either an ER α/β antagonist (ICI 182,780), or a G‐protein‐coupled ER antagonist (G‐15). Using Western blots, only ICI 182,780 prevented the E2‐induced decrease in the α1C subunit expression. Overall, our results suggest that E2 posttranscriptionally downregulates VGCCs via activation of ER α/β; the downregulation is endothelium‐independent. Support: Grant #P20 GM103429‐11.