HYPERCAPNIC VENTILATORY RESPONSES IN MICE DIFFERENTIALLY SUSCEPTIBLE TO ACUTE OZONE EXPOSURE

Susceptibility to ozone (O-3)-induced pulmonary inflammation is greate r in C57BL/6J (B6) than in C3H/HeJ (C3) strain of mice. We tested the hypothesis that altered ventilatory control occurs in B6 mice to a gre ater extent than in C3 mice after acute O-3 exposure. Age-, sex-, and weight-matched C3 and B6 mice were exposed for 3 h to either 2 ppm O-3 or filtered air. One and 24 h after O-3 or air exposure, whole body p lethysmography was used to measure breathing frequency (f), tidal volu me (VT), and minute ventilation (VE). To assess changes in ventilatory control, mice were challenged by the elevation of fractional concentr ation of inspired CO2 levels to 5 and 8% in air for 10 min. After air exposure, there were significantly (P < 0.01) greater changes in VE in B6 than in C3 mice. Hypercapnia-induced changes in VE were significan tly (P < 0.01) attenuated in B6 mice 1 h after O-3 exposure. VT was si gnificantly (P < 0.01) reduced 1 h after O-3 in B6 and C3 mice; howeve r, C3 mice increased f to sustain the hypercapnic VE response similar to air exposure. In contrast, the diminished VT in B6 mice 1 h after O -3 occurred coincident with significantly (P < 0.01) reduced f, mean i nspiratory flow, and slope of VE-to-%CO2 relationship compared with ai r exposure. Altered hypercapnic VE in B6 mice was partially reversed 2 4 h after O-3 relative to air-exposed levels. These data suggest that control of ventilation during phenotypic response to CO2 is governed, in part, by genetic factors in inbred strains of mice. The altered hyp ercapnic ventilatory control caused by acute O-3 exposure varies betwe en strains, implying that there is differential susceptibility with re spect to ventilatory function similar to O-3-induced lung inflammation .