D'Agostino B, Filippelli A, Falciani M, Rossi F, Rossi F
Institute of Pharmacology and Toxicology, Naples, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):561-6. doi: 10.1007/pl00005293.
Endothelins (ETs) are a family of peptide mediators that have a number of biological properties, including the ability to act as potent bronchoconstrictors of isolated human airways. Moreover, elevated concentrations of ET-1 in the bronchoalveolar lavage fluid from patients with symptomatic asthma have also been detected. We investigated the possible contribution of ET-1 in the development of bronchial hyperresponsiveness and the role of inflammatory cell accumulation in rabbit lungs. Our data show that ET-1 challenge to rabbits does not modify basal lung function but results in an increased airway responsiveness to inhaled histamine. Endothelin-treated rabbits were 3-fold (P<0.01) more responsive to inhaled histamine when compared with vehicle-treated rabbits. This hyperresponsiveness was not associated with an alteration in either total or differential inflammatory cell numbers as assessed by bronchoalveolar lavage (BAL). Pre-treatment with capsaicin (80 mg/kg s.c.) did not alter basal lung function or basal responsiveness to inhaled histamine. While capsaicin had no significant effect on the acute bronchoconstriction induced by endothelin-1, this dose was sufficient to significantly inhibit the increase in airway responsiveness to inhaled histamine, achieved 24 h following endothelin-1 challenge. These results indicate that ET-1 may play a role in the development of bronchial hyperresponsiveness to inhaled histamine and that the maintenance of this state is unrelated to a detectable alteration in cellular infiltration within the airway lumen, but probably via the involvement of capsaicin-sensitive nerves.
内皮素（ETs）是一类肽介质，具有多种生物学特性，包括作为离体人气道强效支气管收缩剂的作用。此外，还检测到有症状哮喘患者支气管肺泡灌洗液中ET-1浓度升高。我们研究了ET-1在支气管高反应性发展中的可能作用以及炎症细胞在兔肺中积聚的作用。我们的数据表明，对兔进行ET-1激发不会改变基础肺功能，但会导致气道对吸入组胺的反应性增加。与用赋形剂处理的兔相比，用内皮素处理的兔对吸入组胺的反应性高3倍（P<0.01）。通过支气管肺泡灌洗（BAL）评估，这种高反应性与总炎症细胞数或差异炎症细胞数的改变均无关。用辣椒素（80mg/kg皮下注射）预处理不会改变基础肺功能或对吸入组胺的基础反应性。虽然辣椒素对内皮素-1诱导的急性支气管收缩没有显著影响，但该剂量足以显著抑制内皮素-1激发后24小时出现的气道对吸入组胺反应性的增加。这些结果表明，ET-1可能在对吸入组胺的支气管高反应性发展中起作用，并且这种状态的维持与气道腔内可检测到的细胞浸润改变无关，但可能通过辣椒素敏感神经的参与。
