Tsukagoshi H, Sun J, Kwon O, Barnes P J, Chung K F
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom.
J Appl Physiol (1985). 1995 Mar;78(3):921-7. doi: 10.1152/jappl.1995.78.3.921.
Interleukin-1 beta (IL-1 beta) induces bronchial hyperresponsiveness (BHR) to bradykinin but not to acetylcholine. We examined whether this was mediated through the inhibition of neutral endopeptidase (NEP) activity and/or through the enhancement of airway microvascular leakage (AML) by IL-1 beta. We administered human recombinant IL-1 beta (500 U) or saline intratracheally and 24 h later measured the airway responses to bradykinin (1 mM; 45 breaths). IL-1 beta-treated rats showed a decrease of 18.5 and 21.1% of NEP activity in the lungs and tracheobronchial tree, respectively (P < 0.05), associated with an augmented response in total lung resistance to bradykinin but with no increase in Evans blue dye extravasation used as a marker of AML. Phosphoramidon (0.1 and 1 mM; 90 breaths), an NEP inhibitor, induced a dose-dependent increase in lung resistance to bradykinin without further enhancing BHR induced by IL-1 beta. Bradykinin-induced AML was not enhanced by phosphoramidon in either saline- or IL-1 beta-treated rats. Similarly, after captopril (1 mM; 90 breaths), an inhibitor of angiotensin-converting enzyme, there was no further enhancement of BHR to bradykinin induced by IL-1 beta. BHR to bradykinin induced by IL-1 beta may result from an inhibition of peptidase activity, such as NEP and angiotensin-converting enzyme, and is not associated with an enhancement of AML.
白细胞介素-1β（IL-1β）可诱导支气管对缓激肽产生高反应性（BHR），但对乙酰胆碱无此作用。我们研究了这是否是通过抑制中性内肽酶（NEP）活性和/或通过IL-1β增强气道微血管渗漏（AML）介导的。我们经气管内给予重组人IL-1β（500 U）或生理盐水，24小时后测量气道对缓激肽（1 mM；45次呼吸）的反应。经IL-1β处理的大鼠肺和气管支气管树中的NEP活性分别降低了18.5%和21.1%（P<0.05），这与总肺阻力对缓激肽的反应增强有关，但用作AML标志物的伊文思蓝染料外渗未见增加。NEP抑制剂磷酰胺（0.1和1 mM；90次呼吸）可诱导肺对缓激肽的阻力呈剂量依赖性增加，但不会进一步增强IL-1β诱导的BHR。在生理盐水处理或IL-1β处理的大鼠中，磷酰胺均未增强缓激肽诱导的AML。同样，在给予血管紧张素转换酶抑制剂卡托普利（1 mM；90次呼吸）后，IL-1β诱导的对缓激肽的BHR也未进一步增强。IL-1β诱导的对缓激肽的BHR可能是由于肽酶活性如NEP和血管紧张素转换酶受到抑制，且与AML增强无关。
