Raloxifene relaxes rat intrarenal arteries by inhibiting Ca influx

Leung, Fung Ping, Xiaoqiang Yao, Chi-Wai Lau, WingHung Ko, Limin Lu, and Yu Huang. Raloxifene relaxes rat intrarenal arteries by inhibiting Ca influx. Am J Physiol Renal Physiol 289: F137–F144, 2005. First published February 15, 2005; doi:10.1152/ajprenal.00353.2004.—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 Ca 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 Ca concentration levels ([Ca ]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 raloxifeneor 17 -estradiol-induced relaxation. N-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 [Ca ]i, and raloxifene attenuated this effect. Raloxifene-induced reduction of contraction and increase in VSM [Ca ]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 [Ca ]i in response to CaCl2, indicating that raloxifene relaxes rat renal arteries primarily through inhibiting Ca influx via Ca channels. There is little sex difference in raloxifeneinduced relaxation.