© 1999 American Heart Association, Inc.
Original Contributions |
Antagonistic Effects of 17ß-Estradiol, Progesterone, and Testosterone on Ca2+ Entry Mechanisms of Coronary Vasoconstriction
From the Department of Physiology and Biophysics and The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
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 Ca2+
mobilization into coronary smooth muscle. The effects of
17ß-estradiol, progesterone, and testosterone on vascular reactivity
and 45Ca2+ influx were tested in
deendothelialized coronary artery
strips isolated from castrated male pigs. Prostaglandin
F2
(PGF2) (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 PGF2- and 96
mmol/L KCl-induced contractions with 17ß-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 PGF2- and
KCl-induced 45Ca2+ influx. 17ß-Estradiol
caused similar inhibition of PGF2- and KCl-induced
contractions, suggesting inhibition of the same Ca2+ entry
mechanism. However, progesterone and testosterone caused greater
relaxation of PGF2-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. 17ß-Estradiol mainly inhibits Ca2+
entry, whereas progesterone and testosterone cause coronary
relaxation by inhibiting other mechanisms in addition to
Ca2+ entry.
Key Words: sex hormones • calcium • coronary • contraction
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