Antioxidant transport modulates peripheral airway reactivity and inflammation during ozone exposure

We examined the effects of ozone (O-3) and endogenous antioxidant transport on canine peripheral airway function, central airway function, epithelial integrity, and inflammation Dogs were either untreated or pretreated with p robenecid tan anion-transport inhibitor) and exposed for 6 h to 0.2 parts/m illion O-3 Peripheral airway resistance (Rpa) and reactivity (Delta Rpa) we re monitored in three sublobar locations before and after exposure to eithe r air or O-3. Pulmonary resistance and transepithelial potential difference in trachea and bronchus were also recorded. Bronchoalveolar lavage fluid ( BALF) was collected before, during, and after exposure. O-3 increased Rpa a nd Delta Rpa only in probenecid-treated dogs and in a location-dependent fa shion. Pulmonary resistance and potential difference in bronchus increased after O-3 exposure regardless of treatment. O-3 markedly increased BALF neu trophils only in untreated dogs. With the exception of hexanal, O-3 did not alter any BALF constituent examined. Probenecid reduced BALF ascorbate, BA LF protein, and plasma urate. We conclude that 1) a 6-h exposure to 0.2 par ts/million O-3 represents a subthreshold stimulus in relation to its effect s an peripheral airway function in dogs, 2) antioxidant transport contribut es to the maintenance of normal airway tone and reactivity under conditions of oxidant stress, 3) O-3-induced changes in Rpa and Delta Rpa are depende nt on location, and 4) peripheral airway hyperreactivity and inflammation r eflect independent responses to O-3 exposure. Finally, although anion trans port mitigates the effect of O-3 On peripheral airway function, it contribu tes to the development of airway inflammation and may represent a possible target for anti-inflammatory prevention or therapy.