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.