The nitric oxide-cyclic 3',5'-guanosine monophosphate signal transduction pathway in the mechanism of action of general anesthetics.

Abstract (1) The nitric oxide–cyclic 3′,5′-guanosine monophosphate (NO–cGMP) system is a major signaling transduction pathway implicated in a wide range of physiologic and pathophysiologic functions of the cardiovascular, respiratory, gastrointestinal, nervous or immune systems. (2) Evidence is provided that, at anesthetic concentrations, volatile and intravenous anesthetics interact with the NO–cGMP system. They have been shown to produce a decrease in cGMP in neuronal and vascular tissue. (3) Inhibition of NO synthesis produces a dose-dependent reversible decrease in the minimum anesthetic requirement and in the ED 50 for the loss of righting reflex induced by general anesthetics. Volatile anesthetics also inhibit the NO-mediated relaxation in many vascular beds. (4) The selective alpha-2 adrenergic agonist, dexmedetomidine, which has potent sedative/hypnotic, anesthetic sparing and analgesic properties, produces a dose-dependent, reversible decrease in cGMP in mouse cerebellum at concentrations that decrease the anesthetic requirement of volatile anesthetics or induce a loss of righting reflex, an effect eliminated when NO synthase is inhibited. The site and mechanism by which the anesthetics interact with the NO–cGMP system is not yet clear and may vary with the anesthetic.