QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.077990v1 312/3/1266    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, Y.-C. Articles by Huang, Y. Search for Related Content PubMed PubMed Citation Articles by Chan, Y.-C. Articles by Huang, Y.

CARDIOVASCULAR

Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca²⁺ Influx

Department of Physiology, Chinese University of Hong Kong, Hong Kong, China (Y.-C.C., F.-P.L., X.Y., C.-W.L., Y.H.); and Department of Pharmacology, University of Hong Kong, Hong Kong, China (P.M.V.)

Effects of raloxifene have been documented in the systemic circulation. However, its impact on the pulmonary circulation is unclear. The present study investigated the role of gender, endothelial modulation, and Ca²⁺ channel in relaxations evoked by raloxifene in rat pulmonary arteries and veins. Vascular responses were studied on isolated pulmonary blood vessels mounted in a myograph and constricted by U46619 (9,11-dideoxy-11,9-epoxymethanoprostaglandin F₂). Constrictions to CaCl₂ were studied in Ca²⁺-free, 60 mM K⁺ solution. Changes in the intracellular calcium ion concentration ([Ca²⁺]_i) in vascular smooth muscle were measured using a calcium fluorescence imaging method. Raloxifene was more effective in relaxing U46619-constricted pulmonary arteries from male than female rats. Raloxifene-induced relaxation was unaffected by ICI 182,780 [7-[9-[(4,4,5,5,5,-pentafluoropentyl)-sulfinyl]nonyl]-estra-1,3,5(10)-triene-3,17-diol], inhibition of the nitric oxide (NO) pathway, or removal of the endothelium. In arteries without endothelium, raloxifene attenuated CaCl₂-induced constriction and CaCl₂-stimulated increase in [Ca²⁺]_i with similar potencies. Raloxifene caused endothelium-independent relaxations in pulmonary veins, albeit to a lesser degree than in pulmonary arteries. The venous responses showed a gender difference because raloxifene was more potent in male veins. In summary, raloxifene relaxed rat pulmonary arteries, and this effect did not involve the endothelium/NO or ICI 182,780-sensitive estrogen receptors. Raloxifene, like nifedipine, reduced constriction and [Ca²⁺]_i increase in response to CaCl₂ in high K⁺ solution. Raloxifene also relaxed high K⁺-constricted pulmonary veins. Our data indicate that raloxifene acutely relaxes rat pulmonary blood vessels primarily via inhibition of Ca²⁺ influx through voltage-sensitive Ca²⁺ channels. Finally, raloxifene induced more relaxation in blood vessels isolated from male than female rats.

Address correspondence to: Dr. Yu Huang, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong. E-mail: yu-huang{at}cuhk.edu.hk

This article has been cited by other articles:

				K. A. Bolanz, M. A. Hediger, and C. P. Landowski The role of TRPV6 in breast carcinogenesis Mol. Cancer Ther., February 1, 2008; 7(2): 271 - 279. [Abstract] [Full Text] [PDF]

				C. Pinna, C. Bolego, P. Sanvito, V. Pelosi, R. Baetta, A. Corsini, R. M. Gaion, and A. Cignarella Raloxifene Elicits Combined Rapid Vasorelaxation and Long-Term Anti-Inflammatory Actions in Rat Aorta J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1444 - 1451. [Abstract] [Full Text] [PDF]

				F. P. Leung, X. Yao, C.-W. Lau, W.-H. Ko, L. Lu, and Y. Huang Raloxifene relaxes rat intrarenal arteries by inhibiting Ca2+ influx Am J Physiol Renal Physiol, July 1, 2005; 289(1): F137 - F144. [Abstract] [Full Text] [PDF]