Abstract
We examined the effects of 7-nitroindazole (7-NI) and N-ω-nitro-l-arginine 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) during kainic acid (KA)-induced seizures in newborn
rabbits. After a pre-treatment 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, regional cerebral blood flow (rCBF), cerebral oxygenation
(concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography
(EEG) were continuously monitored throughout the experiment lasting at least 60 min
after the KA administration. There was a significant increase in NO generation in
the brain during KA-induced seizures, which was inhibited by a pre-treatment 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 significant decrease in HbO2 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- and l-NAME-treated animals respectively, than in saline-treated animals. The present data
demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor
cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS)
inhibitor, l-NAME, attenuated both. These findings suggest that NO, probably originating from
eNOS, may play an important 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 damage to the hippocampus.
Keywords
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Article info
Publication history
Accepted:
July 13,
2001
Received in revised form:
May 31,
2001
Received:
February 26,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
