17beta-estradiol increases rat cerebrovascular prostacyclin synthesis by elevating cyclooxygenase-1 and prostacyclin synthase.
OBJECTIVE
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 17beta-estradiol treatment of ovariectomized rats increases cerebrovascular prostacyclin production via elevation of the enzymes responsible for prostacyclin synthesis.


METHODS
Cerebral blood vessels from 17beta-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 17beta-estradiol treatment significantly enhanced basal prostacyclin synthesis in rat cerebral blood vessels by 2.6-fold over control. 17beta-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.
Ospina
Jose A
JA
Department of Pharmacology, College of Medicine, University of California at Irvine, 92697-4625, USA.
Krause
Diana N
DN
Duckles
Sue P
SP
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002469:Cell Separation; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D051545:Cyclooxygenase 1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D013931:Thromboxanes / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D007527:Isoenzymes; D008565:Membrane Proteins; D013931:Thromboxanes; D004958:Estradiol; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase