Differential effects of ozone on airway and tissue mechanics in obese mice

J Appl Physiol (1985). 2004 Jun;96(6):2200-6. doi: 10.1152/japplphysiol.00960.2003. Epub 2004 Feb 13.


Obesity is an important risk factor for asthma. We recently reported increased ozone (O(3))-induced hyperresponsiveness to methacholine in obese mice (Shore SA, Rivera-Sanchez YM, Schwartzman IN, and Johnston RA. J Appl Physiol 95: 938-945, 2003). The purpose of this study was to determine whether this increased hyperresponsiveness is the result of changes in the airways, the lung tissue, or both. To that end, we examined the effect of O(3) (2 parts/million for 3 h) on methacholine-induced changes in lung mechanics with the use of a forced oscillation technique in wild-type C57BL/6J mice and mice obese because of a genetic deficiency in leptin (ob/ob mice). In ob/ob mice, O(3) increased baseline values for all parameters measured in the study: airway resistance (Raw), lung tissue resistance (Rtis), lung tissue damping (G) and elastance (H), and lung hysteresivity (eta). In contrast, no effect of O(3) on baseline mechanics was observed in wild-type mice. O(3) exposure significantly increased Raw, Rtis, lung resistance (Rl), G, H, and eta responses to methacholine in both groups of mice. For G, Rtis, and Rl there was a significant effect of obesity on the response to O(3). Our results demonstrate that both airways and lung tissue contribute to the hyperresponsiveness that occurs after O(3) exposure in wild-type mice. Our results also demonstrate that changes in the lung tissue rather than the airways account for the amplification of O(3)-induced hyperresponsiveness observed in obese mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchial Hyperreactivity / genetics
  • Bronchial Hyperreactivity / physiopathology
  • Female
  • Lung / drug effects
  • Lung / physiology*
  • Lung / physiopathology
  • Male
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Obese
  • Obesity / genetics
  • Obesity / physiopathology*
  • Ozone / pharmacology*


  • Methacholine Chloride
  • Ozone