Consequences of prolonged inhalation of ozone on Fischer-344/N rats: collaborative studies. Part II: Mechanical properties, responses to bronchoactive stimuli, and eicosanoid release in isolated large and small airways.

Acute exposure to ozone has been shown to have deleterious effects on pulmonary function in normal humans and in all animal species studied to date. The goal of this study was to determine whether near-lifetime exposure to ozone alters the mechanical properties, the pharmacologic responses, or both, of airways isolated from F344/N rats, and to relate these properties to airway wall structure. Segments from approximately fourth-generation airways (representing large airways) and eighth-generation airways (representing small airways) were isolated from rats of both genders that had been exposed for six hours per day, five days per week to 0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone for 20 months. Using in vitro techniques, the airways were mounted on myographs and several parameters of airway function were evaluated. These included relationships between (1) passive tension and internal circumference of the airways, (2) active tension and internal circumference of the airways, and (3) responses of the airways to bronchoactive stimuli. The effects on these relationships of epithelial damage caused by lumenal abrasion of selected airway segments also were evaluated. Wall and smooth muscle areas were measured in these airways, and responses obtained from mechanical and pharmacologic studies were related to these morphological parameters. Eicosanoid levels were measured in media surrounding airway explants to determine whether near-lifetime exposure to ozone alters production of these important modulators of airway function. The relation between passive tension and internal circumference found in large and small airways was exponential in nature and unaffected by ozone exposure. The relation between active tension and internal circumference of isolated airways produced a curve characterized by active tension that increased with increasing circumference. This result reached a maximum and then decreased as the circumference increased further. The curve describing this relationship did not change after ozone exposure. The maximum effect was evident at the same point on each airway's passive tension and internal circumference relationship. Wall and smooth muscle areas measured in large airways were not affected by ozone exposure. The wall area increased, however, in small airways isolated from males after exposure to 0.5 ppm ozone. In addition, smooth muscle area increased in small airways isolated from rats exposed to 0.5 ppm ozone; this effect of ozone did not vary with gender. No differences in maximum active stress (active tension normalized to smooth muscle area) were detected in large airways after ozone exposure.(ABSTRACT TRUNCATED AT 400 WORDS)