Effect of hydrogen peroxide on guinea-pig tracheal smooth muscle in vitro: role of cyclo-oxygenase and airway epithelium.

1. Hydrogen peroxide (H2O2) (0.1 microM-3 mM) induced variable contractions of guinea-pig isolated trachea which were attenuated by catalase (100 u ml-1) and mannitol (15 mM) suggesting that contractions were induced by H2O2 and/or the hydroxyl anion. 2. Epithelial removal potentiated contractile responses of tracheal preparations to H2O2 with a leftward shift of the concentration-response curve and an increase in the maximal response. 3. Indomethacin (3 microM) inhibited contractions to H2O2 of intact preparations and preparations without epithelium suggesting that contractions may be mediated by cyclo-oxygenase products. Intact preparations (but not preparations without epithelium) contracted in response to high concentrations (greater than 0.1 mM) of H2O2 in the presence of indomethacin suggesting that other excitatory factor(s) released by the epithelium may induce contraction. 4. Preincubation of intact tracheal preparations with H2O2 (1 mM) for 1 h had no effect on responses to histamine or isoprenaline. 5. These results suggest that hydrogen peroxide generated during the inflammatory process may play a role in bronchoconstriction.