Tsukagoshi H, Haddad E B, Sun J, 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):1015-22. doi: 10.1152/jappl.1995.78.3.1015.
We investigated the role of reactive oxygen species in ozone-induced airway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiveness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were measured in vivo. Neutral endopeptidase (NEP) activity assay and measurement of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-generating NADPH oxidase, was administered perorally 30 min before a 3- or 6-h exposure to 3 ppm of ozone, and the animals were studied 18-24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the increase in airway responsiveness to BK but not to ACh without affecting the neutrophil counts in BALF. The antioxidants allopurinol and deferoxamine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors in vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK receptors in lungs from rats treated with or without apocynin. We conclude that superoxide anions released from inflammatory cells in the airway may be involved in ozone-induced AHR. Inactivation of NEP or upregulation of BK receptors do not appear to be involved, but the possibility of localized changes cannot be excluded.
我们研究了活性氧在臭氧诱导的棕色挪威大鼠气道高反应性（AHR）中的作用。在体内测量了气道对吸入乙酰胆碱（ACh）和缓激肽（BK）的反应性以及支气管肺泡灌洗液（BALF）中炎症细胞的募集情况。在体外进行了中性内肽酶（NEP）活性测定以及棕色挪威大鼠肺中BK受体结合位点的测量。在暴露于3 ppm臭氧3或6小时前30分钟，经口给予5 mg/kg的阿朴吗啡，一种超氧阴离子生成型NADPH氧化酶的抑制剂，并在暴露后18 - 24小时对动物进行研究。臭氧导致气道对ACh和BK的反应性增加以及BALF中中性粒细胞计数增加。阿朴吗啡抑制了气道对BK反应性的增加，但未抑制对ACh反应性的增加，且不影响BALF中的中性粒细胞计数。抗氧化剂别嘌呤醇和去铁胺可预防臭氧诱导的对ACh和BK的AHR，但不降低中性粒细胞计数。为进一步研究臭氧诱导的对BK的AHR机制，我们在臭氧暴露后体外测量了NEP活性和BK受体密度。臭氧暴露对用或未用阿朴吗啡处理的大鼠肺中的NEP活性、BK受体的亲和力和数量均无显著影响。我们得出结论，气道中炎症细胞释放的超氧阴离子可能参与臭氧诱导的AHR。NEP的失活或BK受体的上调似乎未参与其中，但不能排除局部变化的可能性。
