Estrogen and tamoxifen modulate cerebrovascular tone in ovariectomized female rats
Estrogen and tamoxifen modulate cerebrovascular tone in ovariectomized female rats
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DOI：
10.1161/01.hyp.0000131659.27081.19
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发表时间：
2004-07-01
期刊：
影响因子：
8.3
通讯作者：
Huang, Y
中科院分区：
文献类型：
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作者：
Tsang, SY;Yao, XQ;Huang, Y
绝经后雌激素缺乏会增加脑血管疾病的发病率。然而，激素替代疗法与心血管风险增加有关。他莫昔芬是一种选择性雌激素受体调节剂，对心血管危险因素具有雌激素作用，但其对脑血管系统的长期影响尚不清楚。我们假设长期 17β-雌二醇或他莫昔芬治疗在降低卵巢切除大鼠的脑血管张力方面具有类似的作用。因此，我们确定（1）长期17β-雌二醇治疗是否可以影响血管舒缩活动，（2）长期他莫昔芬治疗是否可以发挥雌激素样或雌激素拮抗作用，以及（3）急性暴露于雌激素可以模仿17β-雌二醇的作用。测量雌性大鼠组的脑动脉等长张力：对照组、卵巢切除术、卵巢切除术加17β-雌二醇治疗、卵巢切除术加他莫昔芬治疗、以及用他莫昔芬和17β-雌二醇治疗的卵巢切除大鼠。卵巢切除术增强了脑血管对内皮素-1或CaCl2的收缩，但对U46619或去氧肾上腺素没有增强。 17β-雌二醇疗法逆转了这些影响。长期他莫昔芬治疗通过逆转卵巢切除术引起的血管张力增强而发挥雌激素样作用，而不拮抗长期 17β-雌二醇治疗的效果。卵巢切除术增强了尼卡地平的放松功效，而 17β-雌二醇治疗则阻止了这种效果。急性暴露于10(-9) mol/L 17β-雌二醇或10(-8) mol/L他莫昔芬不会调节未手术雌性大鼠的环收缩。总之，卵巢切除术不同程度地增强了激动剂诱导的脑血管紧张度，而雌激素治疗可以逆转这种作用。他莫昔芬不作为雌激素拮抗剂；相反，它在雌激素缺乏期间充当雌激素激动剂。因此，他莫昔芬可能在脑血管中产生类似于雌激素的有益作用。
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.