Differential estrogen receptor‐mediated Ca2+ regulation in coronary arterial smooth muscle from intact vs. ovariectomized pigs

Abstract

Acute administration of estrogen induces vasodilation in several vascular beds including coronary artery smooth muscle (CSM). We tested the hypothesis that the response of CSM to estrogen is mediated via the binding of estrogen to estrogen receptors (ER) and that the response will be influenced by hormonal status. Coronary smooth muscle was prepared from gonadally intact (INT) and. ovariectomized (OVX) female pigs. Immunocytochemistry and receptor binding assays were performed to confirm presence vs. absence of ER. In INT CSM cells, but not OVX CSM, acute administration of 17β‐estradiol resulted in a concentration‐dependent decrease in [Ca2+]i responses to endothelin‐1. [Ca2+]i responses to 17β‐estradiol were comparable between groups. The effect of 17β‐estradiol was inhibited by the ER antagonist ICI 182,780. 17β‐estradiol decreased [Ca2+]i in INT (but not OVX) CSM cells when sarcoplasmic reticulum (SR) Ca2+ reuptake was inhibited, but to a lesser extent than when extracellular Ca2+ was present. This effect was abolished by extracellular lanthanum. These data suggest that 17β‐estradiol modulates [Ca2+]i in CSM via a likely non‐genomic and necessary ER signaling cascade that mediates both plasma membrane Ca2+ influx and efflux, but does not involve SR Ca2+ release.Supported by NIH grants UL1RR024150‐01(Mayo Clinic CTSA awards to YSP & CMP) and HL74309 (GCS)