Sakamoto T, Tsukagoshi H, Barnes P J, Chung K F
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):387-91. doi: 10.1164/ajrccm.149.2.8306035.
We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide (neurokinin) NK1 and NK2 receptor antagonists, respectively, against bronchoconstriction and airway microvascular leakage induced by inhaled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea. Each antagonist inhibited significantly the maximal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimulation alone.
我们分别研究了新型非肽（神经激肽）NK1和NK2受体拮抗剂CP-96,345和SR-48968对麻醉豚鼠吸入偏亚硫酸氢钠（MBS）所致支气管收缩和气道微血管渗漏的影响。激发后测量6分钟的肺阻力（RL），随后测量伊文思蓝染料向气道组织的渗出情况，以此作为气道微血管渗漏的指标。MBS（80 mM，30次呼吸）导致所有气道水平的RL显著增加以及染料渗漏。CP-96,345（2 mg/kg，静脉注射）而非SR-48968（1.5 mg/kg，静脉注射）能显著抑制除气管外所有气道水平的染料渗漏。每种拮抗剂均能显著抑制RL的最大增加。与单独使用SR-48968相比，联合用药对支气管收缩具有显著的相加作用，并能在与CP-96,345相同的气道水平显著抑制染料渗漏。我们得出结论，吸入MBS所致的支气管收缩至少部分是由NK1和NK2受体的激活介导的，而气道微血管渗漏仅由NK1受体刺激介导。
