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(Stroke. 2002;33:600.)
© 2002 American Heart Association, Inc.

Original Contributions

17ß-Estradiol Increases Rat Cerebrovascular Prostacyclin Synthesis by Elevating Cyclooxygenase-1 and Prostacyclin Synthase

Jose A. Ospina, BS; Diana N. Krause, PhD Sue P. Duckles, PhD

From the Department of Pharmacology, College of Medicine, University of California at Irvine.

Reprint requests to Sue Piper Duckles, PhD, Department of Pharmacology, College of Medicine, University of California at Irvine, Irvine, CA 92697-4625. E-mail spduckle{at}uci.edu

Background and Purpose— It has been reported that estrogens modulate peripheral vascular synthesis of vasodilatory hormones, including prostacyclin. If this occurs in the cerebral circulation, it could have important consequences in the modulation of cerebral hemodynamic function and improvement of stroke outcome. We investigated the hypothesis that in vivo 17ß-estradiol treatment of ovariectomized rats increases cerebrovascular prostacyclin production via elevation of the enzymes responsible for prostacyclin synthesis.

Methods— Cerebral blood vessels from 17ß-estradiol–treated and nontreated ovariectomized rats were isolated and examined for prostacyclin synthesis by enzyme-linked immunosorbent assay or for protein levels of cyclooxygenase-1, prostacyclin-synthase, and cytosolic phospholipase A₂ by immunoblot analysis.

Results— We report that chronic in vivo 17ß-estradiol treatment significantly enhanced basal prostacyclin synthesis in rat cerebral blood vessels by 2.6-fold over control. 17ß-Estradiol treatment also resulted in a 5.1-fold increase of cyclooxygenase-1 protein and a 6.7-fold increase of prostacyclin-synthase protein in the cerebral vasculature. There was no effect of estrogen on levels of cytosolic phospholipase A₂.

Conclusions— Our findings suggest that estrogen influences the biosynthesis of prostacyclin, which may be important in the regulation of cerebral blood flow and thrombosis. This finding may shed light on the mechanisms that govern sex-based differences in cerebrovascular disease.

Key Words: cerebral vessels • estrogens • prostacyclins • prostaglandin endoperoxide-synthase • rats

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