Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage-sensitive Ca2+ channels

被引:36
作者
Tsang, SY
Yao, XQ
Essin, K
Wong, CM
Chan, FL
Gollasch, M
Huang, Y [1 ]
机构
[1] Chinese Univ Hong Kong, Fac Med, Dept Physiol, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Dept Anat, Hong Kong, Hong Kong, Peoples R China
[3] Franz Volhard Clin, Berlin, Germany
[4] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA USA
关键词
vasodilation; cerebrovascular circulation; rats;
D O I
10.1161/01.STR.0000131479.08005.ca
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Because of their mixed estrogen-agonist and estrogen-antagonist properties, selective estrogen receptor modulators (SERMs) are considered promising substitutes for hormone replacement therapy. Raloxifene and other SERMs confer estrogen-like cardiovascular protective effects but lack the carcinogenic activity of exogenous estrogen. However, little is known about the cerebrovascular action of raloxifene. Therefore, we studied the effects of raloxifene on the mechanisms regulating rat cerebral artery tone. Methods and Results-Ring segments of the isolated rat posterior communicating cerebral arteries were mounted in a microvessel myograph for measurement of isometric tension. Whole-cell L-type voltage-sensitive Ca2+ currents were recorded using the perforated patch-clamp technique. Raloxifene (0.1 to 10 mumol/L) reduced the contractile responses to U46619, phenylephrine, and endothelin-1 in normal Krebs solution or to CaCl2 in Ca2+-free, high K+-containing solution. Raloxifene-induced relaxation was identical in endothelium-intact and endothelium-denuded rings. ICI 182780 had no effect on raloxifene-induced relaxation. Raloxifene reduced L-type Ca2+ currents with a pD(2) of 5.98+/-0.06, close to that (6.44+/-0.09) for raloxifene-induced relaxation of 60 mmol/L K+-contracted rings. Conclusions-This study demonstrates that raloxifene acutely relaxes rat cerebral arteries largely via an endothelium-independent mechanism, involving inhibition of Ca2+ influx through L-type Ca2+ channels.
引用
收藏
页码:1709 / 1714
页数:6
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