We have investigated the effects of chlorpheniramine, atropine and capsaicin pretreatment on inhaled sodium metabisulphite (MBS)-induced airway microvascular leakage and bronchoconstriction in anaesthetized guinea-pigs in order to clarify the mechanisms involved in these responses. The effects of frusemide and nedocromil sodium were also examined. 2. Lung resistance (RL) was measured for 6 min after inhalation of MBS (20, 40, 80 and 200 mM; 30 breaths), followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS caused an increase in RL and leakage of dye at all airway levels in a dose-dependent manner. 3. Chlorpheniramine (10 mg kg-1, i.v.), atropine (1 mg kg-1, i.v.), their combination or inhaled nedocromil sodium (10 mg ml-1, 7 min) had no effect against the airway microvascular leakage induced by 80 mM MBS (30 breaths). Capsaicin pretreatment (50 mg kg-1, s.c.) caused a significant decrease in the leakage of dye in the main bronchi and inhaled frusemide (10 mg ml-1, 7 min) also in the main bronchi and proximal intrapulmonary airway. 4. Chlorpheniramine, atropine, their combination, capsaicin pretreatment and frusemide, but not nedocromil sodium, inhibited significantly the peak RL induced by 80 mM MBS (30 breaths) by approximately 50%. 5. We conclude that a cholinergic reflex and neuropeptides released from sensory nerve endings may participate in the mechanisms of MBS-induced airway responses. Frusemide but not nedocromil sodium may have an inhibitor effect on these neural mechanisms. The inhibitory effect of nedocromil sodium against lower doses of MBS is not excluded.
摘要
我们研究了氯苯那敏、阿托品和辣椒素预处理对麻醉豚鼠吸入焦亚硫酸钠（MBS）诱导的气道微血管渗漏和支气管收缩的影响，以阐明这些反应的相关机制。同时也检测了呋塞米和奈多罗米钠的作用。2. 吸入MBS（20、40、80和200 mM；30次呼吸）后测量肺阻力（RL）6分钟，随后测量伊文思蓝染料渗入气道组织的情况，以此作为气道微血管渗漏的指标。MBS在所有气道水平均以剂量依赖方式导致RL增加和染料渗漏。3. 氯苯那敏（10 mg kg-1，静脉注射）、阿托品（1 mg kg-1，静脉注射）、它们的组合或吸入奈多罗米钠（10 mg ml-1，7分钟）对80 mM MBS（30次呼吸）诱导的气道微血管渗漏均无作用。辣椒素预处理（50 mg kg-1，皮下注射）使主支气管中染料渗漏显著减少，吸入呋塞米（10 mg ml-1，7分钟）也使主支气管和肺内近端气道中染料渗漏减少。4. 氯苯那敏、阿托品、它们的组合、辣椒素预处理和呋塞米，但不包括奈多罗米钠，可使80 mM MBS（30次呼吸）诱导的RL峰值显著降低约50%。5. 我们得出结论，胆碱能反射和感觉神经末梢释放的神经肽可能参与MBS诱导的气道反应机制。呋塞米而非奈多罗米钠可能对这些神经机制有抑制作用。不排除奈多罗米钠对较低剂量MBS的抑制作用。
