Published Online
on May 20, 2004

A more recent version of this article appeared on July 1, 2004

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Submitted on February 6, 2004
Revised on March 17, 2004
Accepted on March 31, 2004

Raloxifene Relaxes Rat Cerebral Arteries In Vitro and Inhibits L-Type Voltage-Sensitive Ca²⁺ Channels

Suk-Ying Tsang PhD; Xiaoqiang Yao PhD; Kirill Essin BSc; Chi-Ming Wong BSc; Franky L. Chan PhD; Maik Gollasch MD, PhD; and Yu Huang PhD^*

From Department of Physiology (S.Y.T., X.Y., C.M.W., Y.H.), Chinese University of Hong Kong, China; Department of Anatomy (F.L.C.), Chinese University of Hong Kong, China; Franz Volhard Clinic (K.E., M.G.), Berlin, Germany; and Department of Physiology (K.E., M.G.), LSU Health Sciences Center, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: yu-huang{at}cuhk.edu.hk.

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 µmol/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 pD₂ 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.

Key words: vasodilation • cerebrovascular circulation • rats

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