Sakamoto T, Elwood W, Barnes P J, Chung K F
Department of Thoracic Medicine, National Heart and Lung Institute, London, U.K.
Eur J Pharmacol. 1992 Mar 31;213(3):367-73. doi: 10.1016/0014-2999(92)90625-e.
We have investigated the effect of a new bradykinin receptor antagonist, Hoe 140 (D-Arg- Hyp3,Thi5,D-Tic7,Oic8]-bradykinin), on bradykinin- and platelet-activating factor (PAF)-induced bronchoconstriction and airway microvascular leakage in anesthetized guinea pigs. Extravasation of Evans blue dye and lung resistance were measured simultaneously. Both i.v. (15 nmol/kg) and inhaled bradykinin (1 mM, 45 breaths) caused a significant increase in lung resistance and leakage of dye at all airway levels. Hoe 140 (100 nmol/kg i.v.) almost completely inhibited these airway responses induced by bradykinin except for dye extravasation in trachea induced by inhaled bradykinin. Inhaled PAF (3 mM, 30 breaths) significantly increased lung resistance and leakage of due at all airway levels, but Hoe 140 had no effect on these responses. Bradykinin-induced bronchoconstriction and airway microvascular leakage are predominantly mediated by activation of B2 receptor, since Hoe 140 is a B2 receptor antagonist. Bradykinin receptor-mediated mechanisms do not play an important role on inhaled PAF-induced bronchoconstriction and microvascular leakage.
我们研究了一种新型缓激肽受体拮抗剂Hoe 140（D-精氨酸- Hyp3，Thi5，D- Tic7，Oic8]-缓激肽）对麻醉豚鼠中缓激肽和血小板活化因子（PAF）诱导的支气管收缩及气道微血管渗漏的影响。同时测量伊文思蓝染料外渗和肺阻力。静脉注射（15 nmol/kg）和吸入缓激肽（1 mM，45次呼吸）均导致所有气道水平的肺阻力显著增加和染料渗漏。Hoe 140（静脉注射100 nmol/kg）几乎完全抑制了缓激肽诱导的这些气道反应，但吸入缓激肽诱导的气管染料外渗除外。吸入PAF（3 mM，30次呼吸）显著增加了所有气道水平的肺阻力和染料渗漏，但Hoe 140对这些反应无影响。缓激肽诱导的支气管收缩和气道微血管渗漏主要由B2受体激活介导，因为Hoe 140是一种B2受体拮抗剂。缓激肽受体介导的机制在吸入PAF诱导的支气管收缩和微血管渗漏中不起重要作用。
