Influence of hydroxyl radical on rabbit airway smooth muscle chronically exposed to H2O2 in vivo.

The effects of .OH on the isolated tracheal smooth muscles (TSM), from control, polyethylene glycol (PEG)-glucose oxidase (GO)-, and GO+PEG catalase-treated rabbits were investigated. GO or GO+catalase were given intravenously each week for 4 mo. .OH produced relaxation of basal and ACh-precontracted tension in TSM of control rabbits. The relaxant effect was attenuated by removal of epithelium, whereas it was converted to contraction in the indomethacin-pretreated muscle. .OH produced contraction of TSM and ACh-precontracted muscle in GO-treated rabbits. The contractile response was abolished in preparations denuded of epithelium or pretreated with indomethacin. .OH produced relaxation in basal tension, but a small contraction in ACh-precontracted muscle of GO+catalase-treated rabbits. The contractile response to .OH was unaffected by indomethacin pretreatment; however, it was converted to relaxation in the preparations denuded of epithelium. Contractile response of TSM to ACh was augmented in deepithelialized, indomethacin-, or GO-treated preparations. H2O2 damaged the tracheal epithelium. These results suggest that 1) .OH-induced relaxation/contraction of TSM is partly epithelium dependent and is mediated by bronchodilator/bronchoconstrictor arachidonic acid metabolites, 2) the airway smooth muscle with healthy epithelium responds to .OH differently from those with dysfunctional or damaged epithelium, and 3) hyperresponsiveness of the airways to ACh may be related to the epithelial dysfunction.