INHALATIONAL ANESTHETIC EFFECTS ON RAT CEREBELLAR NITRIC-OXIDE AND CYCLIC GUANOSINE-MONOPHOSPHATE PRODUCTION

Background: Inhalational anesthetics interact with the nitric oxide-cy clic guanosine monophosphate (NO-cGMP) pathway in the central nervous system (CNS) and attenuate excitatory neurotransmitter-induced cGMP co ncentration. The site of anesthetic action on the NO-cGMP pathway in t he CNS remains controversial. This study investigated the effect of in halational anesthetics on N-methyl-D-aspartate (NMDA)-stimulated NO sy nthase activity and cyclic cGMP production in rat cerebellum slices. M ethods: The interaction of inhalational anesthetics with NO synthase a ctivation and cGMP concentration was determined in cerebellum slices o f 10-day-old rats. Nitric oxide synthase activity in cerebellum slices was assessed by measuring the conversion of L-[H-3]arginine to L-[H-3 ]citrulline. The cGMP content of cerebellum slices was measured by rad ioimmunoassay. Results: Isoflurane at 1.5% and 3% enhanced the NMDA-st imulated NO synthase activity by two times while halothane at 1.5% and 3% produced no significant effect. However, the NMDA-stimulated cGMP production was inhibited by both anesthetic agents. The anesthetic inh ibition of cGMP accumulation was not significantly altered by a mixtur e of superoxide dismutase and catalase or by glycine, a coagonist of t he NMDA receptor. Conclusions: The enhancement of NMDA-induced NO synt hase activity by isoflurane and the inhibition of NMDA-stimulated cGMP production by halothane and isoflurane suggests that inhalational ane sthetics interfere with the neuronal NO-cGMP pathway. This inhibitory effect of anesthetics on cGMP accumulation is not due to either their interaction with the glycine binding site of the NMDA receptor or to t he action of superoxide anions.