17 beta-Estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery.
BACKGROUND
We wished to investigate the possible mechanism of the protective effect of estrogen replacement on coronary atherosclerosis observed in postmenopausal women.


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 17 beta-estradiol. Pretreatment with 17 beta-estradiol (30 nmol/L to 30 mumol/L) inhibited the sustained elevation of [Ca2+]i and the sustained contraction induced by 300 nmol/L U46619. Higher concentrations of 17 beta-estradiol (1 to 100 mumol/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+, 17 beta-estradiol (30 mumol/L) inhibited the increases in [Ca2+]i and contraction to resting levels. In contrast, 30 mumol/L 17 beta-estradiol only partially inhibited the U46619-induced sustained contraction, despite complete inhibition of the sustained increase in [Ca2+]i. Verapamil (10 mumol/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 mumol/L 17 beta-estradiol did not show an additional inhibitory effect on either the [Ca2+]i or the tension after the addition of verapamil. 17 beta-Estradiol (10 mumol/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, 17 beta-estradiol did not change the slope of the [Ca2+]i-tension curves. 17 beta-Estradiol (10 mumol/L) had no effect on the levels of cAMP and cGMP in the coronary strips.


CONCLUSIONS
17 beta-Estradiol inhibits the contraction of coronary vascular smooth muscle mainly inhibiting Ca2+ influx without changing Ca2+ sensitivity of contractile elements. The Ca2+ channel blocker-like action of 17 beta-estradiol may explain at least a part of the antiatherosclerotic effect of estrogen.
Han
S Z
SZ
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Karaki
H
H
Ouchi
Y
Y
Akishita
M
M
Orimo
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D004958:Estradiol; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011188:Potassium; D002118:Calcium