Mechanisms and modulatory factors of airway hypersensitivity

(A)在基础实验中；电刺激非肾上腺素能非胆碱能(NANC)抑制神经引起的扩张效应和注入血管活性肠肽(VIP)对猫的即刻气道反应均有明显抑制作用。用丝氨酸蛋白酶抑制剂预处理后，这些抑制作用消失。相反，肾上腺素能神经的扩张作用不受抗原攻击的影响，肾上腺素能神经在猫呼吸道中的分布与NaNC抑制神经的分布相同。综上所述，变应原攻击导致NANC抑制神经舒缩作用的损害可能是由于VIP的降解所致，VIP是该物种NANC抑制神经的候选神经递质。在猫原位模型中，静注缓激肽可引起对乙酰胆碱的高反应性。缓激肽诱导的气道超敏反应的机制可能与气道水肿有关。在豚鼠呼吸道，K通道开放剂NPY和异丁司特抑制神经源性炎症。抑制物的作用方式为突触前水平。IL-1可增强豚鼠的晚期呼吸道反应。氧自由基通过刺激肥大细胞引起支气管收缩。(B)临床研究；1)。ACE增强男性对缓激肽的咳嗽反应。在哮喘患者中，缓激肽通过感觉神经肽的释放引起支气管收缩反应。

(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.