(Circulation. 1995;91:2619-2626.)
© 1995 American Heart Association, Inc.
Articles |
17ß-Estradiol Inhibits Ca2+ Influx and Ca2+ Release Induced by Thromboxane A2 in Porcine Coronary Artery
Presented in part at the 15th Scientific Meeting of the International Society of Hypertension, Melbourne, Australia, March 22, 1994.
From the Department of Geriatrics, Faculty of Medicine, and Department of Veterinary Pharmacology, Faculty of Agriculture (H.K.), University of Tokyo, Japan.
Correspondence to Shu-Zhong Han, MD, PhD, Department of Geriatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan.
Background We wished to investigate the possible mechanism of the protective effect of estrogen replacement on coronary atherosclerosis observed in postmenopausal women.
Methods and Results Cytosolic Ca2+ concentration ([Ca2+]i) and contraction were measured simultaneously in fura 2–loaded porcine coronary arterial strips stimulated by the thromboxane A2 analogue U46619 and high-K+ depolarization in the presence and absence of 17ß-estradiol. Pretreatment with 17ß-estradiol (30 nmol/L to 30 µmol/L) inhibited the sustained elevation of [Ca2+]i and the sustained contraction induced by 300 nmol/L U46619. Higher concentrations of 17ß-estradiol (1 to 100 µmol/L) also inhibited the U46619-induced transient increase in [Ca2+]i and contraction in the absence of extracellular Ca2+. In the strips precontracted by 90 mmol/L K+, 17ß-estradiol (30 µmol/L) inhibited the increases in [Ca2+]i and contraction to resting levels. In contrast, 30 µmol/L 17ß-estradiol only partially inhibited the U46619-induced sustained contraction, despite complete inhibition of the sustained increase in [Ca2+]i. Verapamil (10 µmol/L) also strongly inhibited the sustained increase in [Ca2+]i induced by 300 nmol/L U46619, with a partial inhibition of the U46619-induced sustained contraction. A subsequent addition of 30 µmol/L 17ß-estradiol did not show an additional inhibitory effect on either the [Ca2+]i or the tension after the addition of verapamil. 17ß-Estradiol (10 µmol/L) also inhibited the increase in [Ca2+]i and the contraction induced by cumulative addition of Ca2+ in the strips pretreated with 90 mmol/L K+. However, 17ß-estradiol did not change the slope of the [Ca2+]i-tension curves. 17ß-Estradiol (10 µmol/L) had no effect on the levels of cAMP and cGMP in the coronary strips.
Conclusions 17ß-Estradiol inhibits the contraction of coronary vascular smooth muscle mainly by inhibiting Ca2+ influx without changing Ca2+ sensitivity of contractile elements. The Ca2+ channel blocker–like action of 17ß-estradiol may explain at least a part of the antiatherosclerotic effect of estrogen.
Key Words: hormones • calcium • thromboxane • arteries
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