acute exposure to ozone causes airway obstruction and increased airway reactivity as occurs in asthma. Daily exposure to ozone reduces the effect of subsequent acute exposure to ozone. Ozone may exert some of its effects via the local bronchopulmonary c-fiber reflex system which causes airway edema, bronchoconstriction, and mucus secretion via release of tachykinins. This proposal will study whether acute ozone exposure enhances the activity of the local C-fiber reflex, thereby protecting the distal airways from ozone damage; and if daily exposure diminishes the activity of this system resulting in less physiologic changes, but more damage to distal airways. In these studies, the isolated perfused guinea pig lungs and rhesus monkey intermediate lobes will be exposed to ozone (0.2 to 0.8 ppm) for 1 hour and measurements will be made of pulmonary function, microvascular leak, tachykinin release, tachykinin metabolizing enzymes, tachykinin receptors, and morphometry of epithelial cell injury, C-fiber volume and location, and Evans blue dye extravasation. Specific protocols will examine whether ozone 1) decreases tachykinin metabolism, 2) stimulates C-fiber endings either directly or via mediators which are generated/released, 3)increases tachykinin release, and/or 4) upregulates tachykinin receptors. The final protocol will study whether daily ozone exposure leads to a down-regulation of this system and loss of protection to the distal airways.
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