17-BETA-ESTRADIOL INHIBITS CA2+ INFLUEX AND CA2+ RELEASE INDUCED BY THROMBOXANE A(2) IN PORCINE CORONARY-ARTERY

被引:144
作者
HAN, SZ [1 ]
KARAKI, H [1 ]
OUCHI, Y [1 ]
AKISHITA, M [1 ]
ORIMO, H [1 ]
机构
[1] UNIV TOKYO, FAC AGR, DEPT VET PHARMACOL, BUNKYO KU, TOKYO 113, JAPAN
关键词
HORMONES; CALCIUM; THROMBOXANE; ARTERIES;
D O I
10.1161/01.CIR.91.10.2619
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 A(2) 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 mu mol/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 mu mol/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 mu mol/L) inhibited the increases in [Ca2+](i) and contraction to resting levels. In contrast, 30 mu mol/L 17 beta-estradiol only partially inhibited the U46619-induced sustained contraction, despite complete inhibition of the sustained increase in [Ca2+](i). Verapamil (10 mu mol/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 mu mol/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 mu mol/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 mu mol/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 by 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.
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收藏
页码:2619 / 2626
页数:8
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