Effects of estrogen on postischemic pial artery reactivity to ADP.
OBJECTIVE
The aims of this work were to determine if 1) ischemia alters pial artery responsiveness to the partially nitric oxide (NO)-dependent dilator, ADP, 2) the alteration depends on 17beta-estradial (E2), and 3) NO contributes to E2 protective effects.


METHODS
Response to ADP and the non-NO-dependent dilator, PGE(2), were examined through closed cranial windows. Ovariectomized (OVX) and E2-replaced (E25, 0.025 mg; or E50, 0.05 mg) rats were subjected to 15-minute forebrain ischemia and one-hour reperfusion. Endothelial NO synthase (eNOS) expression was determined in pre- and postischemic isolated cortical microvessels.


RESULTS
In OVX rats, ischemia depressed pial responses to ADP, but not to PGE(2). Both doses of E2 maintained responses to ADP and had no effect on the response to PGE(2). eNOS inhibition decreased the ADP response by 60% in the E25 rats and 50% in the E50 rats, but had no effect in the OVX rats. Compared to the OVX group, microvessel expression of eNOS was increased by E2, but postischemic eNOS was unchanged in both groups.


CONCLUSIONS
The nearly complete loss of postischemic dilation to ADP suggests that normal non-NO-mediated dilatory mechanisms may be acutely impaired after ischemic injury. Estrogen's protective action on ADP dilation may involve both NO- and non-NO-mediated mechanisms.
Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Min
M
Li
Emil
E
Zeynalov
Xiaoling
X
Li
Chikao
C
Miyazaki
Raymond C
RC
Koehler
Marguerite T
MT
Littleton-Kearney
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002536:Cerebral Arteries / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
D004967:Estrogens; D009569:Nitric Oxide; D004958:Estradiol; D000244:Adenosine Diphosphate; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D015232:Dinoprostone