title: Decreased [Ca(2+)](i) during inhibition of coronary smooth muscle contraction by 17beta-estradiol, progesterone, and testosterone.
abstract: The clinical observation that coronary heart disease is more common in men and postmenopausal women than in premenopausal women has suggested cardiovascular protective effects of female sex hormones including hormone-mediated coronary vasodilation. We investigated whether the sex hormones induced coronary relaxation is due to a decrease in [Ca(2+)](i) as measured in single coronary smooth muscle cells isolated from gonadectomized male and female pigs. In the presence of external Ca(2+), prostaglandin F(2alpha) (PGF(2alpha); 10(-5) M) and membrane depolarization by 51 mM KCl caused significant cell contraction and maintained increase in [Ca(2+)](i) to 297 +/- 4 and 341 +/- 20 nM, respectively. At 10(-9) to 6 x 10(-7) M, 17beta-estradiol, progesterone, and testosterone caused inhibition of PGF(2alpha)- and KCl-induced contraction and [Ca(2+)](i) with 17beta-estradiol being most effective. 17alpha-Estradiol did not affect PGF(2alpha)-induced contraction, and the inhibition of PGF(2alpha) contraction by 17beta-estradiol, progesterone, or testosterone was abolished by tamoxifen and ICI 182, 780, RU-486, or flutamide, respectively. 17beta-Estradiol caused similar inhibition of PGF(2alpha)- and KCl-induced contraction and [Ca(2+)](i). Progesterone and testosterone caused greater inhibition of PGF(2alpha)-induced cell contraction and [Ca(2+)](i) compared with the KCl responses. In Ca(2+)-free (2 mM EGTA) solution, caffeine (10 mM) and carbachol (10(-5) M), which activate Ca(2+) release from intracellular stores, caused small cell contraction and transiently increased [Ca(2+)](i) to 256 +/- 53 and 262 +/- 32 nM, respectively. Sex hormones did not significantly affect caffeine- or carbachol-induced contraction or [Ca(2+)](i). Thus, 17beta-estradiol, progesterone, and testosterone cause relaxation of coronary smooth muscle cells and decrease [Ca(2+)](i) mainly by inhibiting Ca(2+) entry from extracellular space but not Ca(2+) release from intracellular stores. The differences in potency of sex hormones in reducing cell contraction and [Ca(2+)](i) suggest differences in the sensitivity of the PGF(2alpha)- and depolarization-activated Ca(2+) entry pathways to inhibition by sex hormones.
authors.affiliation: Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Murphy
authors.forename: R A
authors.initials: RA
authors.lastname: Khalil
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011374:Progesterone / Q000494:pharmacology; D012727:Sex Characteristics; D013552:Swine; D013739:Testosterone / Q000494:pharmacology
chemical_list: D012739:Gonadal Steroid Hormones; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D002118:Calcium