Decreased [Ca2+](i) during inhibition of coronary smooth muscle contraction by 17 beta-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 cardiova scular protective effects of female sex hormones including hormone-mediated coronary vasodilation. We investigated whether the sex hormones induced co ronary relaxation is due to a decrease in [Ca2+](i) as measured in single c oronary smooth muscle cells isolated from gonadectomized male and female pi gs. In the presence of external Ca2+, prostaglandin F-2 alpha (PGF(2 alpha) ;10(-5) M) and membrane depolarization by 51 mM KCl caused significant cell contraction and maintained increase in [Ca2+](i) to 297 +/- 4 and 341 +/- 20 nM, respectively. At 10(-9) to 6 x 10(-7) M, 17 beta-estradiol, progeste rone, and testosterone caused inhibition of PGF(2 alpha)- and KCl-induced c ontraction and [Ca2+](i) with 17 beta-estradiol being most effective. 17 al pha-Estradiol did not affect PGF(2 alpha)-induced contraction, and the inhi bition of PGF(2 alpha) contraction by 17 beta-estradiol, progesterone, or t estosterone was abolished by tamoxifen and ICI 182,780, RU-486, or flutamid e, respectively. 17 beta-Estradiol caused similar inhibition of PGF(2 alpha )- and KCl-induced contraction and [Ca2+](i). Progesterone and testosterone caused greater inhibition of PGF(2 alpha)-induced cell contraction and [Ca 2+](i) compared with the KCl responses. In Ca2+-free (2 mM EGTA) solution, caffeine (10 mM) and carbachol (10(-5) M), which activate Ca2+ release from intracellular stores, caused small cell contraction and transiently increa sed [Ca2+](i) to 256 +/- 53 and 262 +/- 32 nM, respectively. Sex hormones d id not significantly affect caffeine- or carbachol-induced contraction or [ Ca2+](i). Thus, 17 beta-estradiol, progesterone, and testosterone cause rel axation of coronary smooth muscle cells and decrease [Ca2+](i) mainly by in hibiting Ca2+ entry from extracellular space but not Ca2+ release from intr acellular stores. The differences in potency of sex hormones in reducing ce ll contraction and [Ca2+](i) suggest differences in the sensitivity of the PGF(2 alpha)- and depolarization-activated Ca2+ entry pathways to inhibitio n by sex hormones.