Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway

To study the possible role of reactive oxygen species in airway hyperreacti vity, we examined the effects of the superoxide anion radical (O-2(-)) gene rating systems, pyrogallol and xanthine with xanthine oxidase, on muscle to ne, excitatory and inhibitory neurotransmission in the cat airway. Smooth m uscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoke d by electrical field stimulation (EFS) were measured before or after O-2(- ) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane poten tial or excitatory junction potential (EJP) were also measured in vitro. Bo th pyrogallol and xanthine/xanthine oxidase produced biphasic changes in ba sal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both system s consistently produced a prolonged contraction, thereby indicating that O- 2(-) was converted to H2O2 by the action of SOD and as a result the actions of O-2(-) were lost but those of H2O2 introduced. The O-2(-) showed no sig nificant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppre ssion of the contraction and EJP. DEDTCA pretreatment ameliorated the inhib itory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxa tion, probably because O-2(-) could combine with endogenous NO to form pero xynitrite. These results indicate that the O-2(-) generating systems have m ultiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O-2(-) and H2O2). While H2O 2 seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O-2(-) inhibits muscle tone, cholinergic and NANC neurotransmission. (C) 2000 Elsevier Science B.V. All rights reser ved.