Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca 2+ Entry Mechanisms of Coronary Vasoconstriction

Abstract

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 Ca 2+ mobilization into coronary smooth muscle. The effects of 17β-estradiol, progesterone, and testosterone on vascular reactivity and 45 Ca 2+ influx were tested in deendothelialized coronary artery strips isolated from castrated male pigs. Prostaglandin F 2α (PGF 2α ) (10 −5 mol/L) caused significant, maintained contraction of coronary artery strips. Caffeine (25 mmol/L), an activator of Ca 2+ release from intracellular stores, caused transient contraction in Ca 2+ -free solution whereas membrane depolarization by 96 mmol/L KCl, an activator of Ca 2+ entry, caused maintained contraction in the presence of external Ca 2+ . The 3 sex hormones caused significant and concentration-dependent relaxation of PGF 2α - and 96 mmol/L KCl-induced contractions with 17β-estradiol being the most effective. The sex hormones did not significantly affect the transient caffeine contraction in Ca 2+ -free solution. In contrast, the sex hormones significantly inhibited the PGF 2α - and KCl-induced 45 Ca 2+ influx. 17β-Estradiol caused similar inhibition of PGF 2α - and KCl-induced contractions, suggesting inhibition of the same Ca 2+ entry mechanism. However, progesterone and testosterone caused greater relaxation of PGF 2α -induced contraction than of KCl-induced contraction. We conclude that in coronary arteries of castrated male pigs, sex hormones inhibit Ca 2+ entry from extracellular space but not Ca 2+ release from intracellular stores. 17β-Estradiol mainly inhibits Ca 2+ entry, whereas progesterone and testosterone cause coronary relaxation by inhibiting other mechanisms in addition to Ca 2+ entry.