Antagonistic effects of 17 beta-estradiol, progesterone, and testosterone on Ca2+ entry mechanisms of coronary vasoconstriction.
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.
Crews
J K
JK
Department of Physiology, The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Khalil
R A
RA
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*
D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D015237:Dinoprost; D002118:Calcium