Inhalational anesthetic effects on rat cerebellar nitric oxide and cyclic guanosine monophosphate production.
BACKGROUND
Inhalational anesthetics interact with the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway in the central nervous system (CNS) and attenuate excitatory neurotransmitter-induced cGMP concentration. The site of anesthetic action on the NO-cGMP pathway in the CNS remains controversial. This study investigated the effect of inhalational anesthetics on N-methyl-D-aspartate (NMDA)-stimulated NO synthase activity and cyclic cGMP production in rat cerebellum slices.


METHODS
The interaction of inhalational anesthetics with NO synthase activation and cGMP concentration was determined in cerebellum slices of 10-day-old rats. Nitric oxide synthase activity in cerebellum slices was assessed by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. The cGMP content of cerebellum slices was measured by radioimmunoassay.


RESULTS
Isoflurane at 1.5% and 3% enhanced the NMDA-stimulated 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 inhibition of cGMP accumulation was not significantly altered by a mixture of superoxide dismutase and catalase or by glycine, a coagonist of the NMDA receptor.


CONCLUSIONS
The enhancement of NMDA-induced NO synthase activity by isoflurane and the inhibition of NMDA-stimulated cGMP production by halothane and isoflurane suggests that inhalational anesthetics 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 the action of superoxide anions.
Rengasamy
A
A
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Pajewski
T N
TN
Johns
R A
RA
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000493:pharmacokinetics; D002531:Cerebellum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D002956:Citrulline / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis*; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014316:Tritium
D018685:Anesthetics, Inhalation; D018690:Excitatory Amino Acid Agonists; D014316:Tritium; D002956:Citrulline; D009569:Nitric Oxide; D016202:N-Methylaspartate; D001120:Arginine; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D006221:Halothane