OZONE-INDUCED AIRWAY HYPERRESPONSIVENESS - ROLE OF SUPEROXIDE ANIONS,NEP, AND BK RECEPTORS

We investigated the role of reactive oxygen species in ozone-induced a irway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiv eness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammat ory cell recruitment in bronchoalveolar lavage fluid (BALF) were measu red in vivo. Neutral endopeptidase (NEP) activity assay and measuremen t of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-gen erating NADPH oxidase, was administered perorally 30 min before a 3- o r 6-h exposure to 3 ppm of ozone, and the animals were studied 18-24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the incre ase in airway responsiveness to BK but not to ACh without affecting th e neutrophil counts in BALF. The antioxidants allopurinol and deferoxa mine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors i n vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK recept ors in lungs from rats treated with or without apocynin. We conclude t hat superoxide anions released from inflammatory cells in the airway m ay be involved in ozone-induced AHR. Inactivation of NEP or upregulati on of BK receptors do not appear to be involved, but the possibility o f localized changes cannot be excluded.