Abraham W M
Mount Sinai Medical Center, Division of Pulmonary Disease, Miami Beach, Florida 33140.
Agents Actions Suppl. 1992;38 ( Pt 3):439-49.
The potential role of bradykinin and the use of bradykinin antagonists in the treatment of allergic airway disease (asthma) was studied by determining the effects of the bradykinin B2 receptor antagonist, NPC-567 (D-Arg-[Hyp3,D-Phe7]-bradykinin) on antigen-induced early and late bronchial responses, airway inflammation, mediator release and airway hyperresponsiveness in the sheep model of allergic asthma. In the control trial, antigen challenge produced an early bronchoconstrictor response that was associated with an increase in immunoreactive-kinins in bronchoalveolar lavage fluid (BAL), and a late bronchial response that was associated with increased concentrations of leukotriene [LT]B4 and LTC4 and inflammatory cells (neutrophils and eosinophils) in the BAL. Aerosol NPC-567 given before, during and 4 h after antigen challenge had no protective effect on the early bronchoconstrictor response, but significantly inhibited the late bronchial response. This inhibition was correlated with a reduction in the inflammatory lipid mediators and inflammatory cells in BAL. These results suggest that antigen-induced kinin generation may be important for controlling the release of arachidonic acid metabolites from inflammatory cells that contribute to the development of late responses and airway hyperresponsiveness.
通过测定缓激肽B2受体拮抗剂NPC - 567（D - Arg - [Hyp3，D - Phe7] - 缓激肽）对变应性哮喘绵羊模型中抗原诱导的早期和晚期支气管反应、气道炎症、介质释放及气道高反应性的影响，研究了缓激肽的潜在作用以及缓激肽拮抗剂在变应性气道疾病（哮喘）治疗中的应用。在对照试验中，抗原激发产生了早期支气管收缩反应，这与支气管肺泡灌洗液（BAL）中免疫反应性激肽增加相关，以及晚期支气管反应，这与BAL中白三烯[LT]B4和LTC4浓度增加及炎症细胞（中性粒细胞和嗜酸性粒细胞）增多相关。在抗原激发前、激发期间及激发后4小时给予气溶胶NPC - 567，对早期支气管收缩反应无保护作用，但显著抑制了晚期支气管反应。这种抑制与BAL中炎症脂质介质和炎症细胞的减少相关。这些结果表明，抗原诱导的激肽生成可能对控制炎症细胞中花生四烯酸代谢产物的释放很重要，而这些代谢产物有助于晚期反应和气道高反应性的发展。
