To test whether endogenous sensory neuropeptide release results in airway hyperresponsiveness to exogenous bronchoconstrictor stimuli, male Camm- Hartley guinea pigs were exposed either to capsaicin aerosol for 10 min (CAP- AER) or to saline aerosol (SAL-AER) as a control condition. The following day, animals were anesthetized, tracheostomized, and beta-adrenergically blocked with propranolol, and their bronchoconstrictor responses to intravenously administered acetylcholine (ACh), neurokinin A (NKA), or capsaicin were measured. The bronchoconstriction induced by isocapnic dry gas hyperpnea also was assessed. Compared with the SAL-AER control group, the CAP-AER-treated animals exhibited augmented bronchoconstrictor responses to ACh and NKA. In contrast, the SAL-AER and CAP-AER groups had equivalent bronchoconstrictor responses to dry gas hyperpnea and to intravenously administered capsaicin. CAP-AER treatment caused neutrophilic airway inflammation, as reflected in increased numbers of neutrophils in bronchoalveolar lavage fluid obtained from CAP-AER-treated animals. Ablation of airway c-fiber neuron function (by chronic pretreatment with capsaicin prior to capsaicin aerosol inhalation) eliminated the ACh hyperresponsiveness observed in the CAP-AER-treated animals, demonstrating that sensory nerve products play a key role in the development of this nonspecific hyperresponsiveness. Our results demonstrate that sensory nerve stimulation with capsaicin aerosol leads to nonspecific bronchoconstrictor hyperresponsiveness and cellular airway inflammation, and thus disclose another potentially important role of sensory nerves in regulating airway function. Because CAP-AER-treated animals were hyperresponsive to exogenous NKA (a putative mediator of sensory-nerve-induced bronchoconstriction) but not to intravenously administered capsaicin or dry gas hyperpnea (each of which stimulate endogenous sensory nerve tachykinin release), we also conclude that capsaicin aerosol exposure impairs sensory nerve function through an uncertain mechanism.
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