Decreased [Ca(2+)](i) during inhibition of coronary smooth muscle contraction by 17beta-estradiol, progesterone, and testosterone.

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+) 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+) 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+) 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+). Progesterone and testosterone caused greater inhibition of PGF(2alpha)-induced cell contraction and Ca(2+) 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+) to 256 +/- 53 and 262 +/- 32 nM, respectively. Sex hormones did not significantly affect caffeine- or carbachol-induced contraction or Ca(2+). Thus, 17beta-estradiol, progesterone, and testosterone cause relaxation of coronary smooth muscle cells and decrease Ca(2+) 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+) suggest differences in the sensitivity of the PGF(2alpha)- and depolarization-activated Ca(2+) entry pathways to inhibition by sex hormones.