Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea

Exposure to ozone (O-3) enhances airway responsiveness, which is mediated p artly by the release of substance P (SP) from airway neurons. In this study , the role of intrinsic airway neurons in O-3-induced airway responses was examined. Ferrets were exposed to 2 ppm O-3 or air for 1 h. Reactivity of i solated tracheal smooth muscle to cholinergic agonists was significantly in creased after O-3 exposure, as were contractions to electrical field stimul ation at 10 Hz. Pretreatment with CP-99994, a neurokinin type 1 receptor an tagonist, partially abolished the O-3-induced reactivity to cholinergic ago nists and electrical field stimulation. The O-3-enhanced airway responses w ere present in tracheal segments cultured for 24 h, a procedure shown to de plete sensory nerves while maintaining viability of intrinsic airway neuron s, and all the enhanced smooth muscle responses were also diminished by CP- 99994. Immunocytochemistry showed that the percentage of SP-containing neur ons in longitudinal trunk and the percentage of neurons innervated by SP-po sitive nerve fibers in superficial muscular plexus were significantly incre ased at 1 h after exposure to O-3. These results suggest that enhanced SP l evels in airway ganglia contribute to O-3-induced airway hyperresponsivenes s.