Airway hyperresponsiveness to bronchoconstrictor challenge after wood smoke exposure in guinea pigs

Prior airway exposure to wood smoke induces an increase in airway responsiv eness to subsequent smoke inhalation in guinea pigs (Life Sci. 63: 1513, 19 98; 66: 971,2000). To further characterize this airway hyperreactivity, we investigated and compared the airway responsiveness to bronchoconstrictor c hallenge before and 30 min after sham air exposure or wood smoke exposure i n anesthetized and artificially ventilated guinea pigs. Various doses of su bstance P (0.8-6.4 mug/kg), capsaicin (0.2-3.2 mug/kg), prostaglandin F-2 a lpha (30-3000 mug/kg),histamine (1-8 mug/kg), or acetylcholine (5-20 mug/kg ) were intravenously injected at 2-min intervals in successively increasing doses to obtain the dose required to provoke a 200% increase in baseline t otal lung resistance (ED200). Wood smoke exposure significantly lowered the ED200 of substance P, capsaicin, and prostaglandin F-2 alpha whereas sham air exposure failed to do so. Furthermore, wood smoke exposure did not sign ificantly alter the ED200 of histamine or acetylcholine. Pretreatment with phosphoramidon (2 mg/kg), an inhibitor of the neutral endopeptidase (the ma jor degradation enzyme of substance P), before smoke exposure did not signi ficantly affect the smoke-induced reduction in ED200 of substance P. Sectio ning both cervical vagi before smoke exposure did not significantly alter t he smoke-induced reduction in ED200 of capsaicin or prostaglandin F-2 alpha . These results suggest that airway exposure to wood smoke acutely produces airway hyperresponsiveness to substance P, capsaicin, and prostaglandin F- 2 alpha, but not to histamine or acetylcholine. Since the combination of ph osphoramidon and wood smoke exposure did not result in an additive potentia tion of smoke-induced airway hyperresponsiveness to substance Pit is sugges ted that an inhibition of the degradation enzyme of substance P may contrib ute to this increase in airway reactivity. Furthermore, vagally-mediated br onchoconstriction does not play a vital role in enhanced airway responsiven ess to capsaicin or prostaglandin F-2 alpha. (C) 2001 Elsevier Science Inc. All rights reserved.