title: Antagonistic effects of 17 beta-estradiol, progesterone, and testosterone on Ca2+ entry mechanisms of coronary vasoconstriction.
abstract: The clinical observation that coronary artery disease is more common in men and postmenopausal women than in premenopausal women has suggested cardioprotective effects of female sex hormones including hormone-mediated coronary vasodilation. The purpose of this study was to investigate whether the sex hormone-induced coronary relaxation is caused by inhibition of Ca2+ mobilization into coronary smooth muscle. The effects of 17beta-estradiol, progesterone, and testosterone on vascular reactivity and 45Ca2+ influx were tested in deendothelialized coronary artery strips isolated from castrated male pigs. Prostaglandin F2alpha (PGF2alpha) (10(-5) mol/L) caused significant, maintained contraction of coronary artery strips. Caffeine (25 mmol/L), an activator of Ca2+ release from intracellular stores, caused transient contraction in Ca2+-free solution whereas membrane depolarization by 96 mmol/L KCl, an activator of Ca2+ entry, caused maintained contraction in the presence of external Ca2+. The 3 sex hormones caused significant and concentration-dependent relaxation of PGF2alpha- and 96 mmol/L KCl-induced contractions with 17beta-estradiol being the most effective. The sex hormones did not significantly affect the transient caffeine contraction in Ca2+-free solution. In contrast, the sex hormones significantly inhibited the PGF2alpha- and KCl-induced 45Ca2+ influx. 17beta-Estradiol caused similar inhibition of PGF2alpha- and KCl-induced contractions, suggesting inhibition of the same Ca2+ entry mechanism. However, progesterone and testosterone caused greater relaxation of PGF2alpha-induced contraction than of KCl-induced contraction. We conclude that in coronary arteries of castrated male pigs, sex hormones inhibit Ca2+ entry from extracellular space but not Ca2+ release from intracellular stores. 17beta-Estradiol mainly inhibits Ca2+ entry, whereas progesterone and testosterone cause coronary relaxation by inhibiting other mechanisms in addition to Ca2+ entry.
authors: Department of Physiology, The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors: J K
authors: JK
authors: Crews
authors: R A
authors: RA
authors: Khalil
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D013552:Swine; D013739:Testosterone / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D015237:Dinoprost; D002118:Calcium