Effects of estrogen on cerebral blood flow and pial microvasculature in rabbits.
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.
Littleton-Kearney
M T
MT
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. mkearney@jhmi.edu
Agnew
D M
DM
Traystman
R J
RJ
Hurn
P D
PD
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D007261:Infusions, Intra-Arterial; D007322:Instillation, Drug; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D010841:Pia Mater / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004967:Estrogens; D011960:Receptors, Estrogen; D013629:Tamoxifen