INHALATIONAL ANESTHETICS DO NOT ALTER NITRIC-OXIDE SYNTHASE ACTIVITY

Inhalational anesthetics inhibit the nitric oxide (NO)-soluble guanyla te cyclase signaling pathway in vascular and neuronal tissues and it h as been proposed that this inhibition is due to several mechanisms, wh ich include a direct inhibition of NO synthase. To determine the direc t interaction of anesthetics with NO synthase, the effects of halothan e, isoflurane and enflurane on NO synthase activity of bovine and rat brains and cultured bovine aortic endothelial cells were investigated. Halothane and enflurane at 1% to 3% concentrations produced no signif icant effect on crude bovine brain NO synthase activity, as measured b y the conversion of L-[H-3]arginine to L-[H-3]citrulline. Similarly, c rude rat brain NO synthase activity was not affected by exposure to 1% to 4% halothane or isoflurane. The effects of inhalational anesthetic s on the crude bovine brain NO synthase activity were not altered when assayed at two different temperatures (22 degrees C and 37 degrees C) . Halothane and isoflurane produced no significant effects on the acti vity of partially purified rat brain NO synthase at different concentr ations of L-[H-3]arginine in the reaction mixture. Partially purified endothelial NO synthase, when equilibrated with halothane or isofluran e (0.5-2%), exhibited no significant alteration in enzyme activity. Th is study suggests that the effects of inhalational anesthetics on NO s ynthesis in rat and bovine brains and in vascular endothelial cells ar e not due to their direct interaction with NO synthase.