Haxhiu M A, Deal E C, van Lunteren E, Cherniack N S
Department of Medicine, University Hospitals of Cleveland, OH 44106.
J Auton Nerv Syst. 1989 Nov;28(2):105-15. doi: 10.1016/0165-1838(89)90083-0.
Previous studies suggest that structures within 1 mm of the ventral surface of the medulla (VMS) are involved in the regulation of airway resistance. Furthermore, neurons containing tachykinin peptides have been observed near the surface of the VMS. In the present work, we examined the effects of mammalian tachykinins, substance P (SP) and neurokinin A (NKA), applied locally to the intermediate area of the VMS of cats on tracheal tone and phrenic nerve activity. Since neutral endopeptidase (enkephalinase) has been shown to degrade tachykinin peptides in other tissues, we also investigated the effect of the neutral endopeptidase (NEP) inhibitors (thiorphan and phosphoramidon) on airway tone and phrenic nerve responses to tachykinins when the animals were ventilated with 100% O2 and during hyperoxic hypercapnia and isocapnic hypoxia. Experiments were performed in chloralose-anesthetized cats hyperventilated to phrenic neural apnea or so that the end tidal CO2 was just above the apneic threshold. Trachealis smooth muscle tension was assessed by measuring changes in pressure in a balloon placed in a bypassed segment of trachea (Ptseg). Application to the VMS of SP (10(-5)-10(-3) M) significantly increased tracheal muscle tension. Similar effects were found with applications of NKA. In addition, thiorphan and phosphoramidon potentiated the effects of tachykinins and the responses to hypercapnia and hypoxia of tracheal tone and phrenic nerve activity. Pretreatment with atropine (1 mg/kg) blocked tracheal but not phrenic responses to tachykinins. These suggest that (1) tachykinins acting on structures located on the VMS can increase cholinergic outflow to the airways and augment respiratory motor output, and (2) NEP may be one important modulator of tachykinin-induced effects.
先前的研究表明，延髓腹侧面（VMS）1毫米范围内的结构参与气道阻力的调节。此外，在VMS表面附近已观察到含有速激肽的神经元。在本研究中，我们研究了将哺乳动物速激肽、P物质（SP）和神经激肽A（NKA）局部应用于猫VMS中间区域对气管张力和膈神经活动的影响。由于中性内肽酶（脑啡肽酶）已被证明可在其他组织中降解速激肽，我们还研究了中性内肽酶（NEP）抑制剂（硫氧还蛋白和磷酰胺脒）在动物吸入100%氧气、高氧高碳酸血症和等碳酸血症性低氧期间对气道张力和膈神经对速激肽反应的影响。实验在水合氯醛麻醉的猫中进行，使其过度通气至膈神经呼吸暂停，或使呼气末二氧化碳刚好高于呼吸暂停阈值。通过测量置于气管旁路段（Ptseg）的球囊内压力变化来评估气管平滑肌张力。将SP（10⁻⁵ - 10⁻³ M）应用于VMS可显著增加气管肌肉张力。应用NKA也发现了类似的效果。此外，硫氧还蛋白和磷酰胺脒增强了速激肽的作用以及气管张力和膈神经活动对高碳酸血症和低氧的反应。用阿托品（1 mg/kg）预处理可阻断气管对速激肽的反应，但不能阻断膈神经的反应。这些结果表明：（1）作用于VMS上结构的速激肽可增加气道的胆碱能传出并增强呼吸运动输出；（2）NEP可能是速激肽诱导效应的一种重要调节剂。
