Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea.
Wu-ZX; Maize-DF Jr.; Satterfield-BE; Frazer-DG; Fedan-JS; Dey-RD
J Appl Physiol 2001 Jul; 91(1):371-378
Exposure to ozone (O(3)) enhances airway responsiveness, which is mediated partly 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 isolated tracheal smooth muscle to cholinergic agonists was significantly increased after O(3) exposure, as were contractions to electrical field stimulation at 10 Hz. Pretreatment with CP-99994, a neurokinin type 1 receptor antagonist, partially abolished the O(3)-induced reactivity to cholinergic agonists and electrical field stimulation. The O(3)-enhanced airway responses were present in tracheal segments cultured for 24 h, a procedure shown to deplete sensory nerves while maintaining viability of intrinsic airway neurons, and all the enhanced smooth muscle responses were also diminished by CP-99994. Immunocytochemistry showed that the percentage of SP-containing neurons in longitudinal trunk and the percentage of neurons innervated by SP-positive nerve fibers in superficial muscular plexus were significantly increased at 1 h after exposure to O(3). These results suggest that enhanced SP levels in airway ganglia contribute to O(3)-induced airway hyperresponsiveness.
Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment; Respiratory-irritants; Pulmonary-function
R. D. Dey, Dept. of Anatomy, PO Box 9128, West Virginia University, Morgantown, WV 26506
Journal of Applied Physiology