Ichinose M, Miura M, Yamauchi H, Kageyama N, Tomaki M, Oyake T, Ohuchi Y, Hida W, Miki H, Tamura G, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Respir Crit Care Med. 1996 Mar;153(3):936-41. doi: 10.1164/ajrccm.153.3.8630576.
Recent reports suggest the involvement of vascular phenomena in exercise-induced asthma. Sensory neuropeptides, such as substance P (SP), which causes airway vascular dilatation and plasma leakage, have been demonstrated to play a role in hyperpnea-induced airway narrowing in animal studies. The purpose of this study was to investigate the importance of tachykinins in exercise-induced airway narrowing in patients with asthma using a selective neurokinin 1-receptor (NK1-receptor) antagonist, FK-888. In a double-blind, placebo-controlled, crossover trial, nine subjects with stable asthma were given FK-888 (2.5 mg) or placebo by inhalation 20 min before each exercise at a level previously demonstrated to cause a fall of at least 40% in specific airway conduction (SGaw). Inhalation of FK-888 had no significant effect on baseline SGaw. While the recovery from exercise-induced airway narrowing was significantly faster after treatment with FK-888 the area under the curve for SGaw during the 50 min after exercise was significantly reduced (p<0.05) and the time taken for the SGaw to recover to within 65% of baseline after exercise was also significantly shorter with FK-888 than the placebo (p<0.05). However, treatment with FK-888 did not significantly attenuate the maximal fall in SGaw. These results suggest that NK1-receptor-mediated mechanisms are involved in the recovery phase of exercise-induced airway narrowing. The possible mechanisms of these phenomena are discussed.
最近的报告表明血管现象与运动诱发的哮喘有关。在动物研究中，已证实感觉神经肽，如能引起气道血管扩张和血浆渗漏的P物质（SP），在呼吸急促诱发的气道狭窄中起作用。本研究的目的是使用选择性神经激肽1受体（NK1受体）拮抗剂FK-888，研究速激肽在哮喘患者运动诱发的气道狭窄中的重要性。在一项双盲、安慰剂对照、交叉试验中，九名病情稳定的哮喘患者在每次运动前20分钟通过吸入给予FK-888（2.5毫克）或安慰剂，运动强度设定为先前已证明会导致特异性气道传导率（SGaw）至少下降40%。吸入FK-888对基线SGaw无显著影响。虽然FK-888治疗后运动诱发的气道狭窄恢复明显加快，但运动后50分钟内SGaw的曲线下面积显著减小（p<0.05），且FK-888组运动后SGaw恢复至基线的65%以内所需时间也明显短于安慰剂组（p<0.05）。然而，FK-888治疗并未显著减轻SGaw的最大下降幅度。这些结果表明，NK1受体介导的机制参与了运动诱发的气道狭窄的恢复阶段。并对这些现象的可能机制进行了讨论。
