7-Nitro indazole as a selective inhibitor of neuronal NO synthase decreases sevoflurane MAC and cerebellar cMGP content / 中华麻醉学杂志

ABSTRACT

Objective:To examine the effects of acute or chronic administration of 7-nitro indazole (7-NI) on the MAC of sevoflurane and cerebellar cGMP levels in mice. Method:In acute experiment,sevoflurane MAC was determined in mice after 7-NI 120mg/kg, 180mg/kg or 120mg/kg plus L-arginine 600mg/kg was given intraperitoneally. During chronic experiment, MAC was measured on 1st, 4th and 7th day during week-long gavage feeding of 7-NI. The levels of cerebellar cGMP also were measured after acute and chronic administration of 7-NI. Result:Acute administration of 7-NI 120mg/kg decreased sevoflurane MAC by about 20% and cerebellar cGMP level by 96%. 7-NI 180mg/kg did decrease MAC not more than 7-NI 120mg/kg. No significant reduction of MAC was observed in mice treated by intraperitoneal 7-NI 120mg/kg+L-arginine 600mg/kg. In chronic experiment,sevoflurane MAC and cerebellar cGMP were decreased significantly on 1st 4th and 7th day to the similar extend, with 15%-20% reduction in MAC and 46%-60% in cGMP levels. Conclusion:Acute and chronic selective inhibition of nNOS decreases sevoflurane MAC and cerebellar cGMP levels in mice. The maximal reduction (only about 20%) of MAC can be obtained when cGMP levesl are decreased about 50% and further inhibition of generation of cGMP does not produce more enhancement to the potency of sevoflurane anesthesia. No compensatory mechanism for the inhibition of L-Arg-NO-cGMP pathway appears during week-long treatment with 7-NI.