Sakamoto T, Sun J, Barnes P J, Chung K F
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Eur J Pharmacol. 1994 Jan 14;251(2-3):137-42. doi: 10.1016/0014-2999(94)90393-x.
We have investigated the effect of inhaled HOE 140, a novel bradykinin B2 receptor antagonist, against bradykinin- and vagal stimulation-induced airway microvascular leakage and bronchoconstriction in anesthetized guinea-pigs. Lung resistance 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. Bradykinin was given by inhalation (1 mM, 45 breaths) and bilateral vagus nerves were stimulated electrically during a 5-min period (3 and 10 Hz, 5 V, pulse width of 5 ms), both of which caused a significant increase in lung resistance and leakage of dye in the airway. HOE 140 (20 and 200 microM, 60 breaths) completely abolished both the airway effects induced by bradykinin, whereas even the higher dose of HOE 140 had no effect against those induced by electrical vagal stimulation. In conclusion, airway microvascular leakage and bronchoconstriction induced by inhaled bradykinin are mediated by activation of bradykinin B2 receptors in the guinea-pig. In contrast, mechanisms via bradykinin B2 receptors do not play an important role in the acute airway responses induced by vagal stimulation.
我们研究了新型缓激肽B2受体拮抗剂吸入用HOE 140对麻醉豚鼠中缓激肽和迷走神经刺激诱导的气道微血管渗漏及支气管收缩的作用。激发后测量6分钟的肺阻力，随后测量伊文思蓝染料向气道组织的外渗情况，以此作为气道微血管渗漏的指标。通过吸入给予缓激肽（1 mM，45次呼吸），并在5分钟内对双侧迷走神经进行电刺激（3和10 Hz，5 V，脉冲宽度5 ms），这两种操作均导致肺阻力显著增加以及气道染料渗漏。HOE 140（20和200 microM，60次呼吸）完全消除了缓激肽诱导的两种气道效应，而即使是更高剂量的HOE 140对迷走神经电刺激诱导的效应也没有作用。总之，吸入缓激肽诱导的气道微血管渗漏和支气管收缩是由豚鼠体内缓激肽B2受体的激活介导的。相比之下，通过缓激肽B2受体的机制在迷走神经刺激诱导的急性气道反应中并不起重要作用。
