Fluctuation of serum NO(x) concentration at stroke onset in a rat spontaneous stroke model (M-SHRSP). Peroxynitrite formation in brain lesions.
Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) develop hypertension and stroke at earlier ages than do nonmalignant SHRSP. Our previous findings suggested that reactive oxygen species were involved in the development of stroke in this strain. Nitric oxide (NO) which is more released at ischemia, might play a crucial role in stroke development by producing peroxynitrite, a neurotoxic substance. This study investigated whether the development of cerebrovascular lesion in M-SHRSP could be assessed by the fluctuation of serum NO(x) concentration, and whether peroxynitrite is associated with brain damage. Serum NO(x) levels were examined using an automated NO detector. Stroke-onset was temporally assessed according to a known method: changes in body weight, water intake, and neurologic symptoms. Cerebral lesions were confirmed by magnetic resonance imaging (MRI), and Evans blue extravasation at autopsy. MRI taken just after estimated stroke onset disclosed brain lesions. The baseline serum NO(x) level remained at 15-18 micromol/l, but the level gradually increased prior to stroke, and significantly at stroke onset. A marked rise in serum NO(x) occurred subsequently at poststroke. Immunohistochemical staining of nitrotyrosine, a peroxynitrite marker, was detected around vessels, neuronal cells and parenchyma in cerebral lesions. Stroke occurred in 50% of male M-SHRSP at 80 days of age. In conclusion, this study provides the first evidence for fluctuation of serum NO(x) at the onset of spontaneous stroke accompanying the appearance of peroxynitrite in brain lesions. Monitoring serum NO(x) would serve to assess the development of brain lesions at least in spontaneous stroke model.
Tabuchi
Masaki
M
University of Shizuoka, Graduate School of Health Sciences, 52-1, Yada, Shizuoka 422-8526, Japan.
Umegaki
Keizo
K
Ito
Tomohiro
T
Suzuki
Motohisa
M
Tomita
Isao
I
Ikeda
Masahiko
M
Tomita
Takako
T
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D030421:Peroxynitrous Acid / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000097:blood / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine