Nitric oxide mediates brain mitochondrial damage during perinatal anoxia.
The possible role of nitric oxide (.NO) 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 synthesis. Administration of Nomega-nitro-L-arginine monomethyl ester (L-NAME) to the mothers inhibited neonatal brain .NO 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-III damage. Our results suggest that brain mitochondrial dysfunction leading to energy deficiency during perinatal asphyxia is a .NO-mediated process.
Bolaños
J P
JP
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain. jbolanos@gugu.usal.es
Almeida
A
A
Medina
J M
JM
D000818:Animals; D000831:Animals, Newborn; D004734:Energy Metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000473:pathology*; D016014:Linear Models; D008928:Mitochondria / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester