TIME-COURSE OF AIRWAY HYPERRESPONSIVENESS AND REMODELING INDUCED BY HYPEROXIA IN RATS

The purpose of this study was to answer two questions concerning hyper oxia-induced airway hyperresponsiveness: 1) What is the time course of the development of airway hyperresponsiveness? 2) What is the relatio nship between the increase in responsiveness and smooth muscle area? S egments of intrapulmonary bronchi were isolated from male Sprague-Dawl ey rats that had been exposed to 80-85% O-2 for a period of 1, 3, 5, o r 7 days and from aged-matched control animals that breathed room air. Hyperoxia increased the sensitivity (log concentration or frequency t hat elicited a half-maximal response) and reactivity (maximum tension developed) of the airways to electrical field stimulation (EFS) after 3, 5, and 7 days; sensitivity to acetylcholine was not affected, but r eactivity was increased after 7 days. Hyperoxia increased smooth muscl e area beginning 5 days after commencing the exposure. After normalizi ng tension responses to smooth muscle area, reactivity of the airways to the stimuli was not different between the two groups, but sensitivi ty to EFS was still increased. The increase in reactivity observed aft er 5 and 7 days of exposure can be explained by an increase in smooth muscle area that occurred at these time points. The fact that the sens itivity of the airways to EFS remained increased after normalization, together with the fact that the increase in airway responsiveness afte r 3 days of exposure occurred at a time when smooth muscle area was no t different from control, suggests that mechanisms other than increase d smooth muscle area contribute to the development of hyperoxia-induce d airway hyperresponsiveness.