Chronic Exposure to a Simulated Urban Profile of Ozone Alters Ventilatory Responses to Carbon Dioxide Challenge in Rats

Chronic Exposure to a Simulated Urban Profile of Ozone AltersVentilatory Responses to Carbon Dioxide Challenge in Rats. TEPPER,J. S., WIESTER, M. J., WEBER, M. F., FITZGERALD, S., AND COSTA,D. L. (1991). Fundam. Appl. Toxicol. 17, 52–60. Male Fischer344 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, changesin breathing patterns and mechanics in unanesthetized, restrainedrats were observed at Weeks 1,3, 13, 52, and 78 during postexposurechallenge with 0, 4, and 8% carbon dioxide (CO²). The data indicatethat O³ exposure caused an overall increase in expiratory resistance(R^e), but particularly at 78 weeks. This increase in R^e mostlikely accounts for the rats' reduced ability to increase ventilationduring CO² challenge compared to control rats. Reductions inCO²-induced tidal volume increases were observed in all Orexposedanimals during postexposure challenges to 4 and 8% CO². Cumulatively,over all time points, spontaneous frequency of breathing andCO²-induced hyperventilation were also reduced. The decreasein frequency was dependent on a significant increase in theinspiratory time relative to control without a change in expiratorytime. Light microscopic evaluation of the lung did not revealany lesions associated with O³ exposure at any time point. Althoughstatistically significant effects were detected, the etiologyof the above-mentioned functional changes remains speculative.The potential relevance of these data to acute and chronic O³exposure in humans is also discussed.