Chronic smoking enhances tachykinin synthesis and airway responsiveness inguinea pigs

This study tests the hypothesis that the bronchial hyperreactivity induced by chronic cigarette smoke (CS) exposure involves the increased expression and release of tachykinins and calcitonin gene-related peptide (CGRP) from afferent nerve fibers innervating the airways. In guinea pigs chronically e xposed to CS (20 min twice daily for 14-17 d), peak response in total lung resistance to capsaicin (1.68 mug/kg, intravenously) was significantly grea ter than that evoked by the same dose of capsaicin in control (air-exposed) animals. This augmented response in CS-exposed animals was abolished after treatment with CP-99994 and SR-48968, the neurokinin (NK)-1 and NK-2 recep tor antagonists, suggesting the involvement of tachykinins in chronic CS-in duced airway hyperresponsiveness (AHR). Further, substance P (SP)-like immu noreactivity (LI) and CGRP-LI in the airway tissue were significantly great er in the CS animals than in the control animals. Finally, beta -preprotach ykinin (PPT, a splice variant from the PPT A gene encoding tachykinins incl uding SP and NKA) messenger RNA levels as measured by in situ hybridization histochemistry displayed a significant increase in jugular ganglion neuron s but not in dorsal root or nodose ganglion neurons. These data suggest tha t chronic CS-induced AHR is related to an increase in SP synthesis and rele ase in jugular ganglion neurons innervating the lungs and airways.