LACK OF CORRELATION BETWEEN THE REDUCTION OF SEVOFLURANE MAC AND THE CEREBELLAR CYCLIC-GMP CONCENTRATIONS IN MICE TREATED WITH 7-NITROINDAZOLE

Background: Although inhibition of nitric oxide synthase (NOS) has bee n reported to be antinociceptive and to reduce the threshold of genera l anesthesia, the mechanism of action is largely unknown. Specifically , the relation between the minimum alveolar concentration (MAC)-reduci ng effects of NOS inhibition and cyclic guanosine monophosphate (cGMP) concentrations in the brain has not been defined, To further characte rize the effects of NOS inhibition, the authors studied the relation b etween the MAC of sevoflurane and the cGMP concentration of the brain after acute and chronic treatment with a neuronally selective NOS inhi bitor, 7-nitroindazole (7-NI), Methods: Sevoflurane MAC and cerebellar cGMP concentrations were determined in mice after acute intraperitone al 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 separate d into two groups. Sevoflurane;MAC was measured by a tail-clamp method in the first group, and cerebellar cGMP concentrations mere measured by enzyme-linked immunosorbent assay in the second group of the mice. Results: In mice, acute intraperitoneal administration of 7-NI dose de pendently decreased sevoflurane MAC and cerebellar cGMP; and 4-day-lon g gavage feeding with 7-NI (500 mg/kg, every 8 h) time dependently dec reased cerebellar cGMP, but sevoflurane MAC was reduced only for the f irst 2 days and returned to its baseline after 3 days of 7-NI feeding. Conclusions: Although an acute selective inhibition of neuronal NOS d ecreases sevoflurane MAC and cerebellar cGMP concentrations in mice, t here was a dissociation between the two parameters during long-term ne uronal NOS inhibition. There may be cGMP-independent compensatory mech anisms that mediate nociception when NOS is chronically inhibited.