Chronic exposure to a simulated urban profile of ozone alters ventilatory responses to carbon dioxide challenge in rats.

Male Fischer 344 rats were exposed to a simulated urban profile of ozone (O3) (9-hr ramped spike, integrated concentration = 0.19 ppm) for up to 78 weeks. Small, but statistically significant, changes in breathing patterns and mechanics in unanesthetized, restrained rats were observed at Weeks 1, 3, 13, 52, and 78 during postexposure challenge with 0, 4, and 8% carbon dioxide (CO2). The data indicate that O3 exposure caused an overall increase in expiratory resistance (Rc), but particularly at 78 weeks. This increase in Rc most likely accounts for the rats' reduced ability to increase ventilation during CO2 challenge compared to control rats. Reductions in CO2-induced tidal volume increases were observed in all O3-exposed animals during postexposure challenges to 4 and 8% CO2. Cumulatively, over all time points, spontaneous frequency of breathing and CO2-induced hyperventilation were also reduced. The decrease in frequency was dependent on a significant increase in the inspiratory time relative to control without a change in expiratory time. Light microscopic evaluation of the lung did not reveal any lesions associated with O3 exposure at any time point. Although statistically significant effects were detected, the etiology of the above-mentioned functional changes remains speculative. The potential relevance of these data to acute and chronic O3 exposure in humans is also discussed.