Decreased [Ca21]i during Inhibition of Coronary Smooth Muscle Contraction by 17b-Estradiol, Progesterone,

The clinical observation that coronary heart disease is more common in men and postmenopausal women than in premeno-pausal women has suggested cardiovascular protective effects of female sex hormones including hormone-mediated coronary vasodilation. We investigated whether the sex hormones in-duced coronary relaxation is due to a decrease in [Ca21]i as measured in single coronary smooth muscle cells isolated from gonadectomized male and female pigs. In the presence of external Ca21, prostaglandin F2a (PGF2a; 10 25 M) and mem-brane depolarization by 51 mM KCl caused significant cell contraction and maintained increase in [Ca21]i to 297 6 4 and 341 6 20 nM, respectively. At 1029 to 6 3 1027 M, 17b-estradiol, progesterone, and testosterone caused inhibition of PGF2a- and KCl-induced contraction and [Ca 21]i with 17b-estradiol being most effective. 17a-Estradiol did not affect PGF2a-induced contraction, and the inhibition of PGF2a con-traction by 17b-estradiol, progesterone, or testosterone was abolished by tamoxifen and ICI 182,780, RU-486, or flutamide, respectively. 17b-Estradiol caused similar inhibition of PGF2a-and KCl-induced contraction and [Ca21]i. Progesterone and testosterone caused greater inhibition of PGF2a-induced cell contraction and [Ca21]i compared with the KCl responses. In Ca21-free (2 mM EGTA) solution, caffeine (10 mM) and carba-chol (1025 M), which activate Ca21 release from intracellular stores, caused small cell contraction and transiently increased [Ca21]i to 256 6 53 and 262 6 32 nM, respectively. Sex hormones did not significantly affect caffeine- or carbachol-induced contraction or [Ca21]i. Thus, 17b-estradiol, progester-one, and testosterone cause relaxation of coronary smooth muscle cells and decrease [Ca21]i mainly by inhibiting Ca 21 entry from extracellular space but not Ca21 release from intra-cellular stores. The differences in potency of sex hormones in reducing cell contraction and [Ca21]i suggest differences in the sensitivity of the PGF2a- and depolarization-activated C