The proposed research is aimed at testing four specific hypotheses related to the mechanism(s) through which ozone induced lung afferent C fiber excitation serves to protect the small distal airways and alveoli from oxidant injury and inflammation. The specific hypotheses are as follows. 1) In rats, acute inhalation of ozone excites lung C fibers to evoke a rapid shallow breathing pattern, which in turn acts to limit deep lung penetration of ozone and, therefore, reduces ozone induced peripheral airway injury. This hypothesis will be tested by examining the effects of ozone induced reflex changes in breathing pattern and lung mechanics have on the distribution and severity of ozone induced airway after selective blockage of C fibers traversing the vagus nerve. 2) In rats, acute inhalation of ozone will exclusively excite lung C fibers. This will be tested by recording action potentials from all known lung afferents during ozone inhalation. 3). Airway deposition of ozone and subsequent epithelial injury in rats is influenced by breathing pattern. This hypothesis will be tested in paralyzed, normal rats in which breathing frequency is controlled at 80 and 120 breaths/min by negative pressure ventilation and evaluation of nasal, tracheal, proximal bronchial, distal bronchial and terminal bronchiolar airways for 18 oxygen labeled ozone incorporation and airway pathology. 4). Lung C fibers enhance inflammation induced by acute ozone exposure by releasing neuropeptides in airway walls that act to increase airway vascular permeability and the influx of neutrophils. This shall be tested by (a) comparing the effects of ozone inhalation on lung inflammation in normal rats and rats that totally lack sensory C fibers, and (b) comparing lung inflammation following ozone inhalation among several groups of rats, each pretreated with a different neurokinin receptor antagonist. It is anticipated that the information derived from these studies will better define the effects that lung C fibers stimulation evokes during acute ozone exposure.
