Airway Hyperresponsiveness to Cigarette Smoke in Ovalbumin-sensitized Guinea Pigs

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Abstract
This study was carried out to determine if the bronchoconstrictive effect of cigarette smoke (CS) is enhanced when airway hyperresponsiveness is induced by ovalbumin (Ova) sensitization, and if so, whether an increase in endogenously released tachykinins is involved. The bronchoconstrictive ef- fects of an acute CS inhalation challenge (15 ml; 50% concentration) were compared between guinea pigs sensitized with aerosolized Ova and matching control animals (receiving saline aerosol). In Ova-sensitized animals, there were marked increases in the numbers of eosinophils and neutro- phils in the bronchoalveolar lavage fluid (BALF), which was accompanied by an elevated bronchomo- tor response to acetylcholine (ACh). The baseline lung resistance (R L ) and dynamic pulmonary com- pliance (Cdyn) were not significantly different between the two groups; however, the same CS inhalation challenge evoked a significantly more intense bronchoconstriction in the Ova-sensitized group (control group: D R L 5 68 6 8%, D Cdyn 5 2 26 6 6%; Ova group: D R L 5 425 6 76%; D Cdyn 5 2 47 6 8%). The levels of substance P-like immunoreactivity (SP-LI) and calcitonin gene-related pep- tide-like immunoreactivity (CGRP-LI) measured in the bronchoalveolar lavage (BAL) collected after CS inhalation challenge were also significantly greater in Ova-sensitized animals than in control ani- mals. Furthermore, pretreatment with SR-48968, a selective antagonist of neurokinin-2 (NK 2 ) recep- tor, inhibited more than 85% of the enhanced bronchomotor responses to CS challenge, but did not significantly reduce the airway hyperresponsiveness to ACh in Ova-sensitized guinea pigs. These re- sults show that Ova sensitization induces airway hyperresponsiveness to inhaled CS, and that the en- dogenous tachykinins evoked by CS-induced activation of lung C fibers play a primary role in this augmented response. Wu Z-X, Zhou D, Chen G, Lee L-Y. Airway hyperresponsiveness to ciga- rette smoke in ovalbumin-sensitized guinea pigs. AM J RESPIR CRIT CARE MED 2000;161:73-80.