Expression of inducible nitric oxide synthase immunoreactivity in rat brain following chronic hypoxia: effect of aminoguanidine

To clarify the role of inducible nitric oxide synthase (iNOS) in the histopathological changes that occur in the brain after exposure of rats to normobaric hypoxia (10% O-2 in N-2) for 2 weeks, we examined the localization of iNOS and the effect of aminoguanidine, a relatively selective iNOS inhibitor, on the histological outcome. Animals were divided into a hypoxia group, an aminoguanidine-treated hypoxia group and a normoxic control group. The hypoxia group showed severe ischemic changes and prominent angiogenesis in the CA1 hippocampus and cerebral cortex. Aminoguanidine significantly reduced the ischemic change and angiogenesis in these regions, and also reduced iNOS-immunoreactive cells compared to the hypoxia group. These findings suggest that iNOS activity could play a role in the neuropathological alterations induced by chronic hypoxia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.