LUNG INJURY FOLLOWING EXPOSURE OF RATS TO RELATIVELY HIGH-MASS CONCENTRATIONS OF NITROGEN-DIOXIDE

Human inhalation exposures to relatively high mass concentrations of t he oxidant gas nitrogen dioxide (NO2) can result in a variety of pulmo nary disorders, including life-threatening pulmonary edema, pneumonia, and bronchiolitis obliterans. Inasmuch as most experimental studies t o date have examined NO2-induced lung injury following exposures to ne ar ambient or supra-ambient concentrations of NO2, e.g., less than or equal to 50 ppm, little detailed information about the pulmonary injur ious responses following the acute inhalation of higher NO2 concentrat ions that are more commensurate with some actual human exposure condit ions is currently available. Described in this report are the results from a series of investigations in which various aspects of the inhala tion toxicity of high concentrations of NO2 have been examined in labo ratory rats. In the first component of our study, we characterized the kinetic course of development of lung injury following acute exposure s to high concentrations of NO2 delivered over varying durations, and we assessed the relative importance of NO2 exposure concentration vers us exposure time in producing lung injury. For a given exposure durati on, the resulting severity of lung injury was found to generally scale proportionately with inhaled mass concentration, whereas for a given concentration of inhaled NO2, the magnitude of resulting injury was no t directly proportional to exposure duration. Moreover, evidence was o btained that indicated exposure concentration is more important than e xposure time when high concentrations of NO2 are inhaled. In a second component of our investigation, we assessed the pulmonary injurious re sponse that occurs when NO2 is inhaled during very brief, 'high burst' exposures to very high concentrations of NO2. Such exposures resulted in significant lung injury, with the magnitude of such injury being d irectly proportional to exposure concentration. Comparisons of results obtained from this and the first component studies additionally revea led that brief exposures to the very high concentrations of NO2 are mo re hazardous than longer duration exposures to lower concentrations. I n a third study series, we examined pre-exposure, exposure, and post-e xposure modifiers of NO2-induced lung injury, including dietary taurin e, minute ventilation, and post-exposure exercise. Results from these studies indicated: (i) dietary taurine does not protect the rat lung a gainst high concentration NO2 exposure, (ii) the severity of acute lun g injury in response to NO2 inhalation is increased by an increase in minute ventilation during exposure, and (iii) the performance of exerc ise after NO2 exposure can significantly enhance the injurious respons e to NO2. In a final, more mechanistic study component in which we inv estigated the acute hyperpermeability response to high NO2 and the rec ruitment of inflammatory cells into the alveoli, evidence was obtained to suggest that no important relationship exists between the hyperper meability response to NO2 and elevations of polymorphonuclear leukocyt es and alveolar macrophages in the alveoli.