Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part II: Mechanical Properties, Responses to Bronchoactive Stimuli, and Eicosanoid Release in Isolated Large and Small Airways

Research Report 65-II, August 1994

Ozone is a major outdoor air pollutant and short term inhalation can produce temporary chest discomfort, and transient changes in breathing patterns and lung function. Because a large number of people are exposed to levels of ozone sufficient to cause effects on breathing, it is important to understand the short- and long-term consequences of these exposures for human health. Dr. John Szarek\'s study of the effects of prolonged ozone exposure on the contractile and pharmacologic properties of rat airways, which is described in this report, was one of eight studies in the NTP/HEI Collaborative Ozone Project. Dr. Szarek isolated airways from rats that had been exposed to varying ozone concentrations for six hours per day, 5 days per week for 20 months. His objectives were to examine (1) whether the contractile properties of the airway smooth muscle changed after prolonged ozone exposure, and (2) whether prolonged exposure altered the airway muscle\'s response to factors known to affect airway reactivity. Because large and small airways respond differently to inhaled stimuli, he dissected two sizes of airway segments and designated them as large or small. First he measured the tension (force/2 × the airway length) and stress (force/airway wall area) generated in each airway when he stretched them by specific increments. Then he measured the same parameters after stimulating the airways with several drugs or with an electrical field. He also looked for changes in the thickness and amounts of smooth muscle in the airway walls. Finally, he measured the release of eicosanoids, substances that are associated with airway contraction and relaxation. All of these experiments were done in vitro.