Estrogen restores postischemic pial microvascular dilation.
Estrogen protects the brain from experimental cerebral ischemia, likely through both vascular and neuronal cellular mechanisms. The purpose of this study was to determine whether chronic estrogen treatment in males and repletion in ovariectomized (Ovx) females reverses abnormalities in pial arteriolar reactivity during reperfusion from global forebrain ischemia (4-vessel occlusion, 15 min) and whether the site of protection is vascular endothelium. Male and Ovx female rats were implanted with either placebo or a 25-microg 17 beta-estradiol pellet 10 days before ischemia. With the use of intravital microscopy, pial vessel dilation to ACh (10 microM) and S-nitroso-N-acetyl-penicillamine (SNAP; 1 microM) and vasoconstriction to serotonin (10 microM) was examined in situ at 30--60 min of reperfusion. Postischemic changes in vessel diameter were compared with preischemic values for each agent. Postischemic response to both ACh and SNAP was lost in males and Ovx females, but not in estrogen pellet-implanted males and estrogen-implanted Ovx females, suggesting that estrogen protects both endothelial and smooth muscle-mediated vasodilation. Ischemia blunted vessel constriction to serotonin regardless of treatment. These data demonstrate that estrogen acts as a vasoprotective agent within the cerebral circulation and can improve microvascular function under conditions of an acutely evolving ischemic pathology.
Watanabe
Y
Y
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Littleton-Kearney
M T
MT
Traystman
R J
RJ
Hurn
P D
PD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010052:Ovariectomy; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D026423:S-Nitroso-N-Acetylpenicillamine; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D004958:Estradiol; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D000109:Acetylcholine