Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and hippocampal seizures in lesions during kainic acid-induced newborn rabbits

We examined the effects of 7-nitroindazole (7-NI) and. N-omega -nitro-L-arg inine methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to, investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) dur ing kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treat ment with 7-NI (50 mg/kg, i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i .v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, reg ional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of o xyhemoglobin (HbO(2)), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously moni tored throughout the experiment lasting at least 60 min after the KA admini stration. There was a significant increase in NO. generation in the brain d uring KA-induced seizures, which was inhibited by a pretreatment with 7-NI or L-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME. L-NAME pre-treatment caused a signifi cant decrease in HbO(2) and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities, and Neuronal damages in the hippocampus were significantly lower in 7-NI- a nd L-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenua ted neither rCBF nor cerebral oxygenation during the seizures, while the no n-selective NOS (nNOS and eNOS) inhibitor, L-NAME, attenuated both. These f indings suggest that NO, probably originating from eNOS, may play an import ant role in the cerebral circulation. Both 7-NI and L-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less dama ge to the hippocampus. (C) 2001 Elsevier Science B.V. All rights reserved.