HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/F137    most recent 00353.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Leung, F. P. Articles by Huang, Y. Search for Related Content PubMed PubMed Citation Articles by Leung, F. P. Articles by Huang, Y.

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx

¹Department of Physiology, Chinese University of Hong Kong, Hong Kong; and ²Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China

Submitted 16 September 2004 ; accepted in final form 27 January 2005

Raloxifene may confer vascular benefits without causing estrogen-related side effects. However, its action on renal vascular circulation is unknown. This study aimed to examine the sex difference and roles of the endothelium and Ca²⁺ channels in rat renovascular relaxation to raloxifene. On isolated intralobar renal artery rings mounted in a myograph and contracted by U-46619, concentration-relaxation curves were constructed for raloxifene and contractions to CaCl₂ were studied. Changes in intracellular Ca²⁺ concentration levels ([Ca²⁺]_i) of vascular smooth muscle (VSM) were measured by fura 2 fluorescence. Raloxifene or 17-estradiol was equally effective in relaxing renal arteries from both sexes, with raloxifene being more potent than 17-estradiol. Endothelial denudation did not affect raloxifene- or 17-estradiol-induced relaxation. N^G-nitro-L-arginine methyl ester, charybdotoxin plus apamin, indomethacin, or ICI-182, 780 did not modify the effect of raloxifene. Raloxifene caused similar relaxations in rings contracted by U-46619 and high K⁺. Nifedipine attenuated the potency of raloxifene. Raloxifene reduced CaCl₂-induced contractions. K⁺ (80 mM) stimulated an increase in VSM [Ca²⁺]_i, and raloxifene attenuated this effect. Raloxifene-induced reduction of contraction and increase in VSM [Ca²⁺]_i were insensitive to ICI-182, 780. In summary, raloxifene causes relaxation in rat renal arteries; this effect is independent of a functional endothelium and is not mediated by ICI 182, 780-sensitive estrogen receptors. Raloxifene inhibited both contractions and VSM [Ca²⁺]_i in response to CaCl₂, indicating that raloxifene relaxes rat renal arteries primarily through inhibiting Ca²⁺ influx via Ca²⁺ channels. There is little sex difference in raloxifene-induced relaxation.

17-estradiol; relaxation; rat renal artery