title: Estrogen and tamoxifen modulate cerebrovascular tone in ovariectomized female rats.
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 17beta-estradiol or tamoxifen treatment exerted similar effects in reducing cerebrovascular tension in ovariectomized rats. We therefore determine whether (1) chronic 17beta-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 17beta-estradiol. Isometric tension was measured in cerebral arteries from female rat groups: control, ovariectomy, ovariectomy plus 17beta-estradiol treatment, ovariectomy plus tamoxifen treatment, and ovariectomized rats treated with tamoxifen and 17beta-estradiol. Ovariectomy enhanced cerebrovascular contractions to endothelin-1 or CaCl2, but not to U46619 or phenylephrine. 17beta-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 17beta-estradiol treatment. Ovariectomy enhanced the relaxing potency of nicardipine, and 17beta-estradiol treatment prevented this effect. Acute exposure to 10(-9) mol/L 17beta-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.
authors.affiliation: Department of Physiology, Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Suk-Ying
authors.initials: SY
authors.lastname: Tsang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.forename: Franky L
authors.initials: FL
authors.lastname: Chan
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Ismail
authors.initials: I
authors.lastname: Laher
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D010052:Ovariectomy; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol