Antigen-induced airway hyperresponsiveness is associated with airway tissue NEP hypoactivity in rats

In the present study, the role of sensory neuropeptides in the airway hyperresponsiveness (AHR) was investigated. First, the effect of the depletion of sensory neuropeptides by systemic capsaicin treatment on the AHR to acetylcholine (ACh) induced by repeated antigenic challenge to sensitized rats was studied. We secondly investigated whether the neutral endopeptidase (NEP) activity was altered at the antigen-induced AHR. Male Wistar rats were sensitized and repeatedly challenged with DNP-Ascaris antigen. Twenty-four hours after the last antigenic challenge, a marked AHR to inhaled ACh (0.001-0.03%) was observed. This AHR was significantly attenuated by systemic capsaicin pretreatment prior to sensitization. On the other hand, in normal rats, the airway responsiveness to inhaled ACh was significantly increased by pretreatment with NEP inhibitor, phosphoramidon (3 mg/kg, i.v.), but the NEP inhibitor-induced effect was no more observed in the antigen-induced AHR rats. Furthermore, it was found that the airway NEP activity was significantly decreased at the antigen-induced AHR. These findings suggest that NEP hypoactivity and resultant increased sensory neuropeptides have an important role in the pathogenesis of antigen-induced AHR in rats.