Effects of estrogen on cerebral blood flow and pial microvasculature in rabbits

We tested the hypothesis that intracarotid estrogen infusion increases cere bral blood flow (CBF) in a concentration-dependent manner and direct applic ation of estrogen on pial arterioles yields estrogen receptor-mediated vaso dilation. Rabbits of both genders were infused with estrogen via a branch o f the carotid artery. Estrogen doses of 20 or 0.05 mu g.ml(-1).min(-1) were used to achieve supraphysiological or physiological plasma estrogen levels , respectively. CBF and cerebral vascular resistance were determined at bas eline, during the infusion, and 60-min postinfusion, and effects on pial di ameter were assessed via a cranial window. Pial arteriolar response to estr ogen alone and to estrogen after administration of tamoxifen (10(-7)), an a ntiestrogen drug that binds to both known estrogen receptor subtypes, was t ested. No gender differences were observed; therefore, data were combined f or both males and females. Systemic estrogen infusion did not increase regi onal CBF. Estradiol dilated pial arteries only at concentrations ranging fr om 10(-4)-10(-7) M (P less than or equal to 0.05). Pretreatment with tamoxi fen alone had no effect on arteriolar diameter but inhibited estrogen-induc ed vasodilation (P < 0.001). Our data suggest that estrogen does not increa se CBF under steady-state conditions in rabbits. In the pial circulation, t opically applied estradiol at micromolar concentrations dilates vessels. Th e onset is rapid and dependent on estrogen receptor activation.