BLOCKADE OF NITRIC-OXIDE SYNTHESIS INHIBITS HIPPOCAMPAL HYPEREMIA IN KAINIC ACID-INDUCED SEIZURES

We investigated whether the nitric oxide (NO) synthase inhibitor N-G-n itro-L-arginine methyl ester (L-NAME) affects the cerebrovascular chan ges occurring in seizures induced by kainic acid (KA) in awake, sponta neously breathing rats. Blood flow and tissue PO2 and PCO2 were contin uously and simultaneously measured by mass spectrometry from a cannula chronically implanted into the dorsal hippocampus. L-NAME (20 mg/kg; n = 8) or saline (n = 9) was administered i.p. 30 min prior to i.p. KA (10 mg/kg) injection. L-NAME significantly decreased hippocampal bloo d flow and PO2 and increased mean arterial blood pressure (MABP). In L -NAME-treated rats, seizure activity occurred about 10 min sooner than in control rats, and status epilepticus was inevitably followed by a flat electroencephalogram and sudden death. In contrast, control rats survived KA-induced seizures. Hippocampal blood flow was significantly less elevated during the seizures in L-NAME-treated rats than in cont rol rats (maximal levels, 170 and 450%, respectively, of baseline valu es), though MABP remained significantly higher. Hippocampal PO2 was si gnificantly decreased at all times after KA injection in L-NAME-treate d rats, whereas it remained at or above normoxic levels in control rat s. The present results show that L-NAME markedly attenuates the hippoc ampal blood flow and tissue PO2 changes in response to enhanced metabo lic activity due to limbic seizures and suggest that NO is of major im portance in cerebral blood flow control during KA-induced seizures.