Blockade of Nitric Oxide Synthesis Inhibits Hippocampal Hyperemia in Kainic Acid-Induced Seizures

We investigated whether the nitric oxide (NO) synthase inhibitor N^G-nitro-l-arginine methyl ester (l-NAME) affects the cerebrovascular changes occurring in seizures induced by kainic acid (KA) in awake, spontaneously breathing rats. Blood flow and tissue Po₂ and Pco₂ were continuously 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 blood 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 control rats (maximal levels, 170 and 450%, respectively, of baseline values), though MABP remained significantly higher. Hippocampal Po₂ was significantly decreased at all times after KA injection in l-NAME-treated rats, whereas it remained at or above normoxic levels in control rats. The present results show that l-NAME markedly attenuates the hippocampal blood flow and tissue Po₂ changes in response to enhanced metabolic activity due to limbic seizures and suggest that NO is of major importance in cerebral blood flow control during KA-induced seizures.