Journal of Applied Physiology AJP: Regulatory, Integrative and Comparative Physiology
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J Appl Physiol 91: 371-378, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 1, 371-378, July 2001

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

Zhong-Xin Wu1, David F. Maize Jr.1,3, Brian E. Satterfield1, David G. Frazer2, Jeff S. Fedan2, and Richard D. Dey1

1 Department of Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506; 2 Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505; and 3 Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy at Wilkes University, Wilkes-Barre, Pennsylvania 18766

Exposure to ozone (O3) 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 O3-induced airway responses was examined. Ferrets were exposed to 2 ppm O3 or air for 1 h. Reactivity of isolated tracheal smooth muscle to cholinergic agonists was significantly increased after O3 exposure, as were contractions to electrical field stimulation at 10 Hz. Pretreatment with CP-99994, a neurokinin type 1 receptor antagonist, partially abolished the O3-induced reactivity to cholinergic agonists and electrical field stimulation. The O3-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 O3. These results suggest that enhanced SP levels in airway ganglia contribute to O3-induced airway hyperresponsiveness.

airway smooth muscle; sensory nerves; neurokinin receptors; tachykinins; substance P


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