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Published ahead of print on November 25, 2003, doi:10.1164/rccm.200308-1139OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 499-504, (2004)
© 2004 American Thoracic Society

Passive Smoke Effects on Cough and Airways in Young Guinea Pigs

Role of Brainstem Substance P

Jesse P. Joad, Paul A. Munch, John M. Bric, Samuel J. Evans, Kent E. Pinkerton, Chao-Yin Chen and Ann C. Bonham

Departments of Pediatrics, Pharmacology, and Internal Medicine, School of Medicine; and the Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California at Davis, Davis, California

Correspondence and requests for reprints should be addressed to Jesse P. Joad, M.D., University of California, Davis, Department of Pediatrics, 2516 Stockton Boulevard, Sacramento, CA 95817. E-mail: jpjoad{at}ucdavis.edu

Children raised with extended exposure to environmental tobacco smoke (ETS) experience increased cough and wheeze. This study was designed to determine whether extended ETS exposure enhances citric acid–induced cough and bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor mechanism at the first central synapse of lung afferent neurons, the nucleus tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At 5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus tractus solitarius at a site that produced apnea in response to the glutamate agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS exposure significantly enhanced citric acid–induced cough by 56% and maximal Penh (a measure of airway obstruction) by 43%, effects that were attenuated by the NK-1 receptor antagonist in the nucleus tractus solitarius. We conclude that in young guinea pigs extended exposure to ETS increases citric acid–induced cough and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus tractus solitarius.

Key Words: nucleus tractus solitarius • environmental tobacco smoke • substance P • guinea pig • development




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