Mazzone Stuart B, Canning Brendan J
Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Am J Physiol Regul Integr Comp Physiol. 2002 Jul;283(1):R86-98. doi: 10.1152/ajpregu.00007.2002.
The hypothesis that airway afferent nerve subtypes act synergistically to initiate reflex bronchospasm in guinea pigs was addressed. Laryngeal mucosal application of capsaicin or bradykinin or the epithelial lipoxygenase metabolite 15(S)-hydroxyeicosatetraenoic acid evoked slowly developing but pronounced and sustained increases in tracheal cholinergic tone in situ. These reflexes were reversed by atropine and prevented by vagotomy, trimethaphan, or laryngeal denervation. Central nervous system-acting neurokinin receptor antagonists also abolished the reflexes without altering baseline cholinergic tone. Baseline tone was, however, reversed by disrupting pulmonary afferent innervation while preserving the innervation of the trachea and larynx. Surprisingly, selective pulmonary denervation also prevented the laryngeal capsaicin-induced tracheal reflexes, suggesting that laryngeal C-fibers act synergistically with continuously active intrapulmonary mechanoreceptors to initiate reflex bronchospasm. Indeed, reflex bronchospasm evoked by histamine was markedly potentiated by bradykinin, an effect mimicked by intracerebroventricular, but not intravenous, substance P. These data, as well as anatomic evidence for afferent nerve subtype convergence in the commissural nucleus of the solitary tract, suggest that airway nociceptors and mechanoreceptors may act synergistically to regulate airway tone.
本研究探讨了气道传入神经亚型协同作用引发豚鼠反射性支气管痉挛的假说。向喉黏膜施用辣椒素、缓激肽或上皮脂氧合酶代谢产物15(S)-羟基二十碳四烯酸，可诱发气管胆碱能张力在原位缓慢发展但显著且持续的升高。这些反射可被阿托品逆转，并可通过迷走神经切断术、三甲噻芬或喉去神经支配来预防。作用于中枢神经系统的神经激肽受体拮抗剂也可消除这些反射，而不改变基线胆碱能张力。然而，在保留气管和喉的神经支配的同时破坏肺传入神经支配，可逆转基线张力。令人惊讶的是，选择性肺去神经支配也可预防喉辣椒素诱导的气管反射，提示喉C纤维与持续活跃的肺内机械感受器协同作用，引发反射性支气管痉挛。事实上，缓激肽可显著增强组胺诱发的反射性支气管痉挛，脑室内注射P物质可模拟这一效应，但静脉注射则不能。这些数据，以及孤束连合核中传入神经亚型汇聚的解剖学证据，提示气道伤害感受器和机械感受器可能协同作用来调节气道张力。
