Brain nitric oxide synthase activity is decreased by intravenous anesthetics

Nitric oxide is produced from L-arginine in a variety of cells, and in neuronal tissue, by the action of nitric oxide synthase. Inhibitors to nitric oxide synthase reduce the threshold for anesthesia and anesthetics reduce nitric oxide synthase activity in neutrophils. We investigated the effect of four intravenous anesthetics and an anticonvulsant on rat brain nitric oxide synthase activity using the stoichiometric conversion of oxyhemoglobin to methemoglobin by nitric oxide. Enzyme activity was assayed in the presence of 0, 0.01, 0.1, and 1.00 mu M thiopental, ketamine, etomidate, midazolam, and phenytoin. Thiopental (P = 0.001), ketamine (P = 0.0002), midazolam (P = 0.0024), and etomidate (P = 0.0006) caused a decrease in nitric oxide synthase activity. Phenytoin had no effect on enzyme activity. We conclude that the intravenous anesthetics, but not the nonsedative anticonvulsant tested, have a significant effect on neuronal nitric oxide synthase activity.