Effect of chronically exposing young guinea pigs to environmental tobacco smoke on cough and bronchoconstriction, role of NK-1 receptors in the nucleus tractus solitarius

Abstract Rationale Children raised with exposure to environmental tobacco smoke experience increased cough and wheeze. This study was designed to determine if extended environmental tobacco smoke 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. Methods Guinea pigs were exposed to environmental tobacco smoke (1 mg/m 3 total suspended particulates) 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 neurokinin-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 (n=7 to 10 each group). Statistical analysis was by ANOVA with post hoc analysis consisting of a series of Sheffe contrast tests among the treatment groups as appropriate. Results Environmental tobacco smoke exposure significantly enhanced citric acid-induced cough by 56% ( P =0.03) and maximal Penh (a measure of airway obstruction) by 43% ( P P =0.0003 for cough and P=0.03 for Penh). Conclusions We conclude that in young guinea pigs, extended exposure to environmental tobacco smoke increases citric acid-induced cough and bronchoconstriction in part by an neurokinin-1 receptor mechanism in the nucleus tractus solitarius.