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  • Title: Estrogen and tamoxifen modulate cerebrovascular tone in ovariectomized female rats.
    Author: Tsang SY, Yao X, Chan FL, Wong CM, Chen ZY, Laher I, Huang Y.
    Journal: Hypertension; 2004 Jul; 44(1):78-82. PubMed ID: 15159380.
    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.
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