Daffonchio L, Lees I W, Payne A N, Whittle B J
Br J Pharmacol. 1987 Jul;91(3):701-8. doi: 10.1111/j.1476-5381.1987.tb11265.x.
Anaphylactic bronchoconstriction provoked by aerosol challenge, and its pharmacological modulation, has been investigated in anaesthetized pump-ventilated guinea-pigs actively sensitized to ovalbumin (OA). Aerosol challenge (OA 0.03-10 mg ml-1) provoked immediate bronchoconstriction, the degree of which, and its rate of development, was directly related to antigen concentration. Concomitant changes in heart rate and systemic arterial blood pressure following aerosol challenge were reduced compared with systemic (OA, 1 mg kg-1 i.v.) challenge. Unlike systemic challenge, aerosol challenge did not cause a concomitant fall in either circulating leukocyte or platelet count. When a submaximal (microshock) aerosol challenge stimulus (OA, 0.3 mg ml-1, 5 s) was employed, bronchoconstriction was markedly reduced by mepyramine (2 mg kg-1 i.v.). The residual component of bronchoconstriction was enhanced by indomethacin (10 mg kg-1 i.v.), an effect which was reversed by either BW755C (30 mg kg-1 i.v.) or FPL55712 (10 mg kg-1 i.v.). When a supramaximal (macroshock) aerosol challenge stimulus (OA, 10 mg ml-1, 5 s) was employed, bronchoconstriction was also markedly reduced by mepyramine. Residual bronchoconstriction was not altered by indomethacin, slowed but not reduced by indomethacin plus BW755C, and substantially reduced by indomethacin plus FPL55712. The successive incremental antagonism of anaphylactic bronchoconstriction by mepyramine and mepyramine plus indomethacin and FPL55712 indicates that the predominant mediators involved are histamine and leukotrienes, respectively. The failure of indomethacin plus BW755C to inhibit the mepyramine-resistant bronchoconstriction provoked by OA macroshock may reflect the increased generation of leukotrienes via a 5-lipoxygenase isoenzyme resistant to inhibition by BW755C. 7. Aerosol challenge of actively sensitized anaesthetized guinea-pigs by this method may be a useful model of human allergic bronchoconstriction, particularly when the effects of a drug given itself as an aerosol are being evaluated.
在对卵清蛋白（OA）主动致敏的麻醉状态下经泵通气的豚鼠中，研究了雾化激发引起的过敏性支气管收缩及其药理学调节作用。雾化激发（OA 0.03 - 10 mg/ml）引起即刻支气管收缩，其程度及其发展速率与抗原浓度直接相关。与全身给药（OA，1 mg/kg静脉注射）激发相比，雾化激发后心率和体循环动脉血压的伴随变化较小。与全身给药激发不同，雾化激发不会导致循环白细胞或血小板计数同时下降。当采用次最大（微冲击）雾化激发刺激（OA，0.3 mg/ml，5秒）时，美吡拉敏（2 mg/kg静脉注射）可显著减轻支气管收缩。吲哚美辛（10 mg/kg静脉注射）可增强支气管收缩的残余成分，BW755C（30 mg/kg静脉注射）或FPL55712（10 mg/kg静脉注射）可逆转这一作用。当采用超最大（宏冲击）雾化激发刺激（OA，10 mg/ml，5秒）时，美吡拉敏也可显著减轻支气管收缩。残余支气管收缩不受吲哚美辛影响，吲哚美辛加BW755C可使其减缓但不减轻，吲哚美辛加FPL55712可使其显著减轻。美吡拉敏以及美吡拉敏加吲哚美辛和FPL55712对过敏性支气管收缩的相继递增拮抗作用表明，主要涉及的介质分别是组胺和白三烯。吲哚美辛加BW755C未能抑制OA宏冲击引起的美吡拉敏抵抗性支气管收缩，这可能反映了通过对BW755C抑制有抗性的5-脂氧合酶同工酶生成白三烯的增加。7. 通过这种方法对主动致敏的麻醉豚鼠进行雾化激发，可能是人类过敏性支气管收缩的一种有用模型，特别是在评估以气雾剂形式给药的药物的效果时。
