The expression of nNOS, iNOS and nitrotyrosine is increased in the rat cerebral cortex in experimental hepatic...

The changes in the distribution and amount of nitric oxide (NO) synthases (nNOS and iNOS) and the appearance of nitrotyrosine (NT) in the rat cerebral cortex were investigated following portacaval anastomosis (PCA), an experimental hepatic encephalopathy (HE) model. One month after PCA, rats showed more neurones immunoreactive to nNOS than did control animals. At 6 months post PCA, the number of neurones expressing nNOS had again increased and the intensity of the immunoreactions was stronger. Immunohistochemical analysis also showed that iNOS was increasingly expressed in pyramidal-like cortical neurones and in perivascular astrocytes from 1 to 6 months post PCA. In addition, a significant increase in cerebral iNOS concentration, at both post-PCA periods, was determined by Western blotting. The iNOS induction appears to be correlated with the length of the post-PCA period. PCA also induced the expression of NT, a nitration product of peroxynitrite. NT immunoreactivity was found in pyramidal-like cortical neurones. At 6 months, NT immunoreactivity was also evident in perivascular astrocytes, which was concomitant with a significant increase in NT protein level. PCA therefore not only increases the expression of nNOS but also induces the expression of iNOS and NT in both neurones and astrocytes. Taken together, these findings indicate that the induction of iNOS in pyramidal neurones and cortical astrocytes 6 months after PCA contributes to the generation of NT, and demonstrate the clear participation of NO in the pathogenic process of HE in this model.