7-Nitroindazole attenuates nitrotyrosine formation in the early phase of cerebral ischemia-reperfusion in mice.
The purpose of this study was to evaluate the role of neuronal nitric oxide synthase (nNOS) in nitrotyrosine (NO2-Tyr) formation in the early phase of ischemia-reperfusion in mouse brain. Using a hydrolysis/high pressure liquid chromatography (HPLC) procedure (0.6 microM detection limit), we measured %NO2-Tyr (ratio of NO2-Tyr to total tyrosine) in 23 male C57Black/6J mice subjected to 2-h middle cerebral artery occlusion followed by 0.5-h reperfusion, in the presence (25 or 50 mg/kg) and absence of 7-nitroindazole (7-NI), a relatively specific nNOS inhibitor. At 25 mg/kg, 7-NI reduced NO2-Tyr formation to about a half of that in the vehicle-treated group (0.10 +/- 0.07 vs. 0.18 +/- 0.05%), while 50 mg/kg suppressed NO2-Tyr formation to below the limit of detection, indicating that nNOS is responsible for most of the NO2-Tyr formation in the early phase after reperfusion.
Department of Neurology, Tokai University School of Medicine, Kanagawa, Japan.
H
H
Hirabayashi
S
S
Takizawa
N
N
Fukuyama
H
H
Nakazawa
Y
Y
Shinohara
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D007191:Indazoles; D018696:Neuroprotective Agents; C002744:3-nitrotyrosine; D014443:Tyrosine; C080122:7-nitroindazole