Bergren D R, Ustinova E E, Schultz H D
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha NE 68178, USA.
Respir Physiol. 1997 Feb;107(2):99-109. doi: 10.1016/s0034-5687(96)02515-7.
Inhibition of peptidases within the lungs not only potentiates the effects of neuropeptides released from C-fibers but also the effects of bradykinin and capsaicin both of which stimulate C-fibers. To determine if peptidase inhibition potentiates C-fiber activation, we challenged pulmonary C-fibers in rats with capsaicin or bradykinin before and after inhibition of neutral endopeptidase (NEP) or angiotensin converting enzyme (ACE). Inhibition of NEP by phosphoramidon (10 mg/kg, i.v.) potentiated the effect of capsaicin (0.5-1 micrograms, i.v.) on C-fiber activity but did not change the response to bradykinin (1-2 micrograms, i.v.). Inhibition of ACE by captopril (5 mg/kg, i.v.) potentiated C-fiber activation by either bradykinin or capsaicin. Aerosol administration of either phosphoramidon (1 x 10(-5) M, 2 min) or captopril (4.6 x 10(-3) M, 2 min) potentiated C-fiber activation by capsaicin aerosol (1.6 x 10(-4) M, 1 min) but not by bradykinin aerosol (9.4 x 10(-5) M, 1 min). Therefore, inhibition of NEP or ACE may potentiate airway obstructive mechanisms initiated by C-fiber stimulation.
抑制肺内的肽酶不仅会增强从C纤维释放的神经肽的作用，还会增强缓激肽和辣椒素的作用，这两种物质都会刺激C纤维。为了确定肽酶抑制是否会增强C纤维的激活，我们在抑制中性内肽酶（NEP）或血管紧张素转换酶（ACE）之前和之后，用辣椒素或缓激肽刺激大鼠的肺C纤维。磷酰胺（10毫克/千克，静脉注射）抑制NEP可增强辣椒素（0.5 - 1微克，静脉注射）对C纤维活性的作用，但不会改变对缓激肽（1 - 2微克，静脉注射）的反应。卡托普利（5毫克/千克，静脉注射）抑制ACE可增强缓激肽或辣椒素对C纤维的激活作用。雾化吸入磷酰胺（1×10⁻⁵摩尔，2分钟）或卡托普利（4.6×10⁻³摩尔，2分钟）可增强辣椒素气雾剂（1.6×10⁻⁴摩尔，1分钟）对C纤维的激活作用，但对缓激肽气雾剂（9.4×10⁻⁵摩尔，1分钟）则无此作用。因此，抑制NEP或ACE可能会增强由C纤维刺激引发的气道阻塞机制。
