Inhalational anesthetic effects on rat cerebellar nitric oxide and cyclic guanosine monophosphate production

Appavoo Rengasamy, Thomas N. Pajewski, Roger A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

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 agency. 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.

Original languageEnglish (US)
Pages (from-to)689-698
Number of pages10
JournalAnesthesiology
Volume86
Issue number3
DOIs
StatePublished - Mar 1997
Externally publishedYes

Keywords

  • Anesthetics, inhalational: halothane; isoflurane
  • Cell signaling: nitric oxide; cyclic guanosine monophosphate
  • Neurotransmitters: N-methyl-D-aspartate

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'Inhalational anesthetic effects on rat cerebellar nitric oxide and cyclic guanosine monophosphate production'. Together they form a unique fingerprint.

Cite this