Littleton-Kearney M T, Agnew D M, Traystman R J, Hurn P D
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Am J Physiol Heart Circ Physiol. 2000 Sep;279(3):H1208-14. doi: 10.1152/ajpheart.2000.279.3.H1208.
We tested the hypothesis that intracarotid estrogen infusion increases cerebral blood flow (CBF) in a concentration-dependent manner and direct application of estrogen on pial arterioles yields estrogen receptor-mediated vasodilation. Rabbits of both genders were infused with estrogen via a branch of the carotid artery. Estrogen doses of 20 or 0.05 microg. ml(-1). min(-1) were used to achieve supraphysiological or physiological plasma estrogen levels, respectively. CBF and cerebral vascular resistance were determined at baseline, during the infusion, and 60-min postinfusion, and effects on pial diameter were assessed via a cranial window. Pial arteriolar response to estrogen alone and to estrogen after administration of tamoxifen (10(-7)), an antiestrogen drug that binds to both known estrogen receptor subtypes, was tested. No gender differences were observed; therefore, data were combined for both males and females. Systemic estrogen infusion did not increase regional CBF. Estradiol dilated pial arteries only at concentrations ranging from 10(-4)-10(-7) M (P < or = 0.05). Pretreatment with tamoxifen alone had no effect on arteriolar diameter but inhibited estrogen-induced vasodilation (P < 0.001). Our data suggest that estrogen does not increase CBF under steady-state conditions in rabbits. In the pial circulation, topically applied estradiol at micromolar concentrations dilates vessels. The onset is rapid and dependent on estrogen receptor activation.
颈内动脉注入雌激素以浓度依赖方式增加脑血流量（CBF），且雌激素直接作用于软脑膜小动脉会产生雌激素受体介导的血管舒张。通过颈动脉分支给雌雄兔子注入雌激素。分别使用20或0.05微克·毫升⁻¹·分钟⁻¹的雌激素剂量来达到超生理或生理血浆雌激素水平。在基线、注入期间和注入后60分钟测定CBF和脑血管阻力，并通过颅窗评估对软脑膜直径的影响。测试了软脑膜小动脉对单独雌激素以及对他莫昔芬（10⁻⁷）给药后雌激素的反应，他莫昔芬是一种与两种已知雌激素受体亚型结合的抗雌激素药物。未观察到性别差异；因此，将雄性和雌性的数据合并。全身注入雌激素并未增加局部CBF。雌二醇仅在浓度范围为10⁻⁴ - 10⁻⁷ M时使软脑膜动脉扩张（P≤0.05）。单独用他莫昔芬预处理对小动脉直径无影响，但抑制了雌激素诱导的血管舒张（P < 0.001）。我们的数据表明，在兔子的稳态条件下，雌激素不会增加CBF。在软脑膜循环中，以微摩尔浓度局部应用的雌二醇会使血管扩张。起效迅速且依赖于雌激素受体激活。
