Evidence that estrogen suppresses Rho-kinase function in the cerebral circulation in vivo
Evidence that estrogen suppresses Rho-kinase function in the cerebral circulation in vivo
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DOI：
10.1161/01.str.0000136951.85586.c8
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发表时间：
2004-09-01
期刊：
影响因子：
8.3
通讯作者：
Sobey, CG
中科院分区：
文献类型：
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作者：
Chrissobolis, S;Budzyn, K;Sobey, CG
背景和目的-绝经前女性比男性或绝经后女性更不易患心血管疾病。这种疾病状态通常与血管RhoA/Rho激酶活性增加和一氧化氮（NO）活性降低有关。本研究测试女性性别是否与较低的Rho-激酶活性或较高的NO活性在脑动脉中的体内和雌激素是否有助于任何这样的性别difference.Methods -基底动脉直径的变化进行了测量与使用的颅窗准备在麻醉的Sprague-Dawley大鼠。对一些雌性大鼠进行卵巢切除术（OVX），并每天皮下注射溶剂（二甲基亚砜）或17 β-雌二醇，持续14天。RhoA或Rho激酶的血管表达通过Western blotting.Results进行评估-Rho激酶抑制剂Y-27632在男性中作为脑血管扩张剂的选择性比女性高约3倍。总RhoA或Rho激酶的表达在男性和女性之间没有差异。在OVX大鼠中，对Y-27632的血管舒张反应与雄性大鼠的反应相似。用17 β-雌二醇治疗OVX大鼠使Y-27632的血管舒张作用正常化，与完整雌性对照组的反应相当。一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯引起约50%以上的收缩，基底动脉在女性比男性，但反应在OVX大鼠治疗的车辆或17 β-雌二醇并没有不同于那些记录在完整的females.Conclusions -这些数据表明，血管Rho激酶功能受到抑制，因为女性的影响，雌激素，而女性NO活性的升高与雌激素无关。
Background and Purpose - Premenopausal women are less susceptible to cardiovascular diseases than men or postmenopausal women. Such disease states are often associated with increased vascular RhoA/Rho-kinase activity and decreased activity of nitric oxide ( NO). This study tested whether female gender is associated with lower Rho-kinase activity or higher NO activity in cerebral arteries in vivo and whether estrogen contributes to any such gender differences.Methods - Changes in basilar artery diameter were measured with the use of a cranial window preparation in anesthetized Sprague-Dawley rats. Some female rats were ovariectomized (OVX) and treated subcutaneously daily for 14 days with vehicle ( dimethyl sulfoxide) or 17beta-estradiol. Vascular expression of RhoA or Rho-kinase was assessed by Western blotting.Results - The Rho-kinase inhibitor Y-27632 was selectively approximate to3-fold more potent as a cerebral vasodilator in males versus females. Expression of total RhoA or Rho-kinase did not differ between males and females. In OVX rats, vasodilator responses to Y-27632 resembled responses in males. Treatment of OVX rats with 17beta-estradiol normalized the vasodilator effects of Y-27632 to be equivalent to responses in intact female controls. The NO synthase inhibitor N-nitro-L-arginine methyl ester caused approximate to 50% greater constriction of the basilar artery in females versus males, but responses in OVX rats treated with either vehicle or 17beta-estradiol did not differ from those recorded in intact females.Conclusions - These data indicate that vascular Rho-kinase function is suppressed in females because of the effects of estrogen, whereas the higher NO activity in females is estrogen independent.