Nitric oxide mediates brain mitochondrial damage during perinatal anoxia

The possible role of nitric oxide ((NO)-N-.) in brain energy metabolism during perinatal asphyxia in the rat was studied. Exposure of early neonates to 5 min of anoxia significantly inhibited brain mitochondrial complex II-III activity by 25%, without affecting complex I, complex IV or citrate synthase activities. This insult was accompanied by ATP depletion (54%) and increased concentration of nitrites plus nitrates (1.4-fold), suggesting enhanced (NO)-N-. synthesis. Administration of N-omega-nitro-L-arginine monomethyl ester (L-NAME) to the mothers inhibited neonatal brain (NO)-N-. synthase activity, as reflected by the decreased (23%) cyclic GMP concentration. These L-NAME-treated neonates showed complete resistance to anoxic-mediated brain mitochondrial complex II-In damage. Our results suggest that brain mitochondrial dysfunction leading to energy deficiency during perinatal asphyxia is a (NO)-N-.-mediated process. (C) 1998 Elsevier Science B.V.