7-Nitroindazole, a selective inhibitor of neuronal nitric oxide synthase: effect on sevoflurane MAC and cerebellar cyclic GMP in mice

Purpose Considerable evidence suggests that nitric oxide (NO) plays a role in synaptic transmission in the central and peripheral nervous systems. However, whether inhibition of NO synthesis decreases minimum alveolar concentration (MAC) of inhalational anesthetics is controversial. We examined the effects of 7-nitroindazole (7-NI), a selective inhibitor of neuronal NOS (nNOS), on the MAC of sevoflurane and cerebellar cyclic guanosine monophosphate (cGMP) levels in mice. Methods Sevoflurane MAC and cerebellar cGMP levels were determined in mice after acute intraperitoneal or weeklong gavage feeding of 7-NI. Sevoflurane MAC and cerebellar cGMP levels after chronic treatment were measured on days 1, 4, and 7 and were repeated after an acute intraperitoneal dose of nitro ^g -l-arginine methylester (l-NAME). Results Acute and chronic treatment with 7-NI decreased the sevoflurane MAC by 20%–30%. Reduction of cerebellar cGMP levels was greater after intraperitoneal administration of NOS inhibitors than after gavage feeding of 7-NI. Conclusion Acute or chronic selective inhibition of neuronal NOS decreases the sevoflurane MAC and cerebellar cGMP levels in mice. 7-NI permitted probing of the role of NO in perception of noxious stimuli.