Published Online
on May 24, 2004

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

This Article Full Text (PDF) Data Supplement All Versions of this Article: 44/1/78    most recent 01.HYP.0000131659.27081.19v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsang, S.-Y. Articles by Huang, Y. Search for Related Content PubMed PubMed Citation Articles by Tsang, S.-Y. Articles by Huang, Y. Related Collections Cerebrovascular disease/stroke Animal models of human disease Other Vascular biology Other Research

Submitted on March 26, 2004
Revised on April 13, 2004

Estrogen and Tamoxifen Modulate Cerebrovascular Tone in Ovariectomized Female Rats

Suk-Ying Tsang; Xiaoqiang Yao; Franky L. Chan; Chi-Ming Wong; Zhen-Yu Chen; Ismail Laher; and Yu Huang^*

From the Departments of Physiology (S.-Y.T., X.Y., C.-M.W., Y.H.), Anatomy (F.L.C.), and Biochemistry (Z.-Y.C.), Chinese University of Hong Kong, Hong Kong, China; and Department of Pharmacology and Therapeutics (I.L.), University of British Columbia, Canada.

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

Abstract--Postmenopausal estrogen deficiency increases the incidence of cerebrovascular disease. However, hormone replacement therapy is associated with an increased cardiovascular risk. Tamoxifen is a selective estrogen receptor modulator with estrogenic effects on cardiovascular risk factors, but its long-term impacts on cerebral vasculature are unknown. We hypothesized that chronic 17-estradiol or tamoxifen treatment exerted similar effects in reducing cerebrovascular tension in ovariectomized rats. We therefore determine whether (1) chronic 17-estradiol treatment could influence vasomotor activities, (2) chronic tamoxifen therapy could exert an estrogen-like or estrogen-antagonistic effect, and (3) acute exposure to estrogen could mimic the effect of 17-estradiol. Isometric tension was measured in cerebral arteries from female rat groups: control, ovariectomy, ovariectomy plus 17-estradiol treatment, ovariectomy plus tamoxifen treatment, and ovariectomized rats treated with tamoxifen and 17-estradiol. Ovariectomy enhanced cerebrovascular contractions to endothelin-1 or CaCl₂, but not to U46619 or phenylephrine. 17-Estradiol therapy reversed these effects. Chronic tamoxifen treatment exerted estrogen-like actions by reversing ovariectomy-induced enhancement of vessel tone without antagonizing the effect of chronic 17-estradiol treatment. Ovariectomy enhanced the relaxing potency of nicardipine, and 17-estradiol treatment prevented this effect. Acute exposure to 10^-9 mol/L 17-estradiol or 10^-8 mol/L tamoxifen did not modulate contractions in rings from nonoperated female rats. In conclusion, ovariectomy differentially enhances agonist-induced cerebrovascular tone, an effect that was reversed by estrogen therapy. Tamoxifen does not act as an estrogen antagonist; instead, it functions as an estrogen agonist during estrogen deficiency. Thus, tamoxifen may confer beneficial effects similar to estrogen in cerebrovascular vessels.

Key words: cerebral arteries • estrogen • vasoconstriction • rats

This article has been cited by other articles:

				C. J. Mark, R. Tatchum-Talom, D. S. Martin, and K. M. Eyster Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1969 - R1975. [Abstract] [Full Text] [PDF]

				C. S. Rigsby, A. E. Burch, S. Ogbi, D. M. Pollock, and A. M. Dorrance Intact female stroke-prone hypertensive rats lack responsiveness to mineralocorticoid receptor antagonists Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1754 - R1763. [Abstract] [Full Text] [PDF]

				D. N. Krause, S. P. Duckles, and D. A. Pelligrino Influence of sex steroid hormones on cerebrovascular function J Appl Physiol, October 1, 2006; 101(4): 1252 - 1261. [Abstract] [Full Text] [PDF]

				R. A. Khalil Sex Hormones as Potential Modulators of Vascular Function in Hypertension Hypertension, August 1, 2005; 46(2): 249 - 254. [Abstract] [Full Text] [PDF]

				Y.-C. Chan, F.-P. Leung, X. Yao, C.-W. Lau, P. M. Vanhoutte, and Y. Huang Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca2+ Influx J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1266 - 1271. [Abstract] [Full Text] [PDF]