Mechanisms and modulatory factors of airway hypersensitivity

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(A) In basic experiments ;1). We demonstrated that both dilatory effects induced by electrical stimulation of nonadrenergic noncholinergic (NANC) inhibitory nerves and infused VIP were significantly inhibited after immediate airway response in cats in vivo. These inhibitions disappeared on pretreatment with a serine protease inhibitor. By contrast, the dilatory effects of adrenergic nerves, which are distributed in the same way as NANC inhibitory nerves in cat airways, were not affected after antigen challenge. Taken together, allergen-challenge-induced impairment of the dilatory effect of NANC inhibitory nerves is presumably due to the degradation of VIP, which is a candidate neurotransmitter of NANC inhibitory nerves in this species.2). In cat in situ model, bradykinin infusion caused airway hyperresponsiveness to acetylcholine. The mechanisms of the bradykinin-induced airway hypersensitivity is possibly due to airway edema.3). In guinea-pig airways, K channel opener, NPY, and ibudilast inhibited neurogenic inflammation. The mode of action of the inhibitors were pre-synaptic level.4). IL-1 enhanced late airway response in guinea-pigs.5). Oxygen radicals caused bronchoconstriction via mast cell stimulation.(B) In clinical studies ;1). ACE enhanced cough response to bradykinin in man.2). In asthmatic patients, bradykinin caused bronchoconstrictor response via sensory neuropeptides release.