Lack of correlation between the reduction of Sevoflurane MAC and the cerebellar cyclic GMP concentrations in mice treated with 7-nitroindazole

• Published in: Anesthesiology (Philadelphia) Vol. 89; no. 1; pp. 143 - 148
• Main Authors: ICHINOSE, F, MI, W.-D, MIYAZAKI, M, ONOUCHI, T, GOTO, T, MORITA, S
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01.07.1998
• Subjects: Anesthetics, Inhalation - administration & dosage; Anesthetics, Inhalation - pharmacokinetics; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Cerebellum - metabolism; Cyclic GMP - metabolism; Enzyme Inhibitors - pharmacology; Indazoles - pharmacology; Lung - metabolism; Medical sciences; Methyl Ethers - administration & dosage; Methyl Ethers - pharmacokinetics; Mice; Neuropharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Pharmacology. Drug treatments; Sevoflurane; Volatile compound; Intraperitoneal administration; Enzyme; Rodentia; Oral administration; Enzyme inhibitor; General anesthesia; 3',5'-GMP; Nitric-oxide synthase; Sevoflurane; Vertebrata; Mammalia; General anesthetic; Minimal alveolar concentration; Mouse; Animal; Drug interaction; Oxidoreductases; Fluorine Organic compounds; Brain (vertebrata)
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199807000-00021

Although inhibition of nitric oxide synthase (NOS) has been reported to be antinociceptive and to reduce the threshold of general anesthesia, the mechanism of action is largely unknown. Specifically, the relation between the minimum alveolar concentration (MAC)-reducing effects of NOS inhibition and cyclic guanosine monophosphate (cGMP) concentrations in the brain has not been defined. To further characterize the effects of NOS inhibition, the authors studied the relation between the MAC of sevoflurane and the cGMP concentration of the brain after acute and chronic treatment with a neuronally selective NOS inhibitor, 7-nitroindazole (7-NI). Sevoflurane MAC and cerebellar cGMP concentrations were determined in mice after acute intraperitoneal administration or after 1, 2, 3, and 4 days of gavage feeding of 7-NI. After acute or chronic treatment with 7-NI, the mice were separated into two groups. Sevoflurane MAC was measured by a tail-clamp method in the first group, and cerebellar cGMP concentrations were measured by enzyme-linked immunosorbent assay in the second group of the mice. In mice, acute intraperitoneal administration of 7-NI dose dependently decreased sevoflurane MAC and cerebellar cGMP; and 4-day-long gavage feeding with 7-NI (500 mg/ kg, every 8 h) time dependently decreased cerebellar cGMP, but sevoflurane MAC was reduced only for the first 2 days and returned to its baseline after 3 days of 7-NI feeding. Although an acute selective inhibition of neuronal NOS decreases sevoflurane MAC and cerebellar cGMP concentrations in mice, there was a dissociation between the two parameters during long-term neuronal NOS inhibition. There may be cGMP-independent compensatory mechanisms that mediate nociception when NOS is chronically inhibited.