Hypercapnic ventilatory responses in mice differentially susceptible to acute ozone exposure.
Susceptibility to ozone (O3)-induced pulmonary inflammation is greater 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 greater extent than in C3 mice after acute O3 exposure. Age-, sex-, and weight-matched C3 and B6 mice were exposed for 3 h to either 2 ppm O3 or filtered air. One and 24 h after O3 or air exposure, whole body plethysmography was used to measure breathing frequency (f), tidal volume (VT), and minute ventilation (VE). To assess changes in ventilatory control, mice were challenged by the elevation of fractional concentration 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 significantly (P < 0.01) attenuated in B6 mice 1 h after O3 exposure. VT was significantly (P < 0.01) reduced 1 h after O3 in B6 and C3 mice; however, 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 O3 occurred coincident with significantly (P < 0.01) reduced f, mean inspiratory flow, and slope of VE-to-%CO2 relationship compared with air exposure. Altered hypercapnic VE in B6 mice was partially reversed 24 h after O3 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tankersley
C G
CG
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Fitzgerald
R S
RS
Mitzner
W A
WA
Kleeberger
S R
SR
D000818:Animals; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*; D010641:Phenotype; D010993:Plethysmography, Whole Body; D015656:Respiratory Mechanics / Q000502:physiology*; D013045:Species Specificity; D013990:Tidal Volume / Q000502:physiology
D010126:Ozone