Sadeghi-Hashjin G, Folkerts G, Henricks P A, Verheyen A K, van der Linde H J, van Ark I, Coene A, Nijkamp F P
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, the Netherlands.
Am J Respir Crit Care Med. 1996 May;153(5):1697-701. doi: 10.1164/ajrccm.153.5.8630623.
Peroxynitrite (ONOO-) is a cytotoxic product of the rapid reaction between nitric oxide and superoxide that may initiate inflammation. Isolated perfused tracheas from guinea pigs were incubated from the mucosal side for 15 min with peroxynitrite (1 to 100 muM). Thereafter, concentration-response curves to histamine and methacholine were constructed on the preparations. Peroxynitrite (10 muM) caused a significant hyperresponsiveness; the maximal contractions in response to histamine and methacholine were enhanced by 30% and 40%, respectively. In the peroxynitrite-treated group, clear epithelial damage as well as eosinophil destruction were detected. Moreover, 3, 5, and 10 days after intratracheal instillation of peroxynitrite (100 nmol), a significant rise in pulmonary resistance to histamine of anesthetized animals was observed. It is suggested that the generation of peroxynitrite from nitric oxide superoxide radicals during inflammatory processes induces epithelial damage, mediator release, and hence airway hyperresponsiveness. These findings may have clinical implications, because airway inflammation, epithelial damage, and hyperresponsiveness are characteristic features in patients suffering from asthma.
过氧亚硝酸根（ONOO-）是一氧化氮和超氧阴离子快速反应产生的一种细胞毒性产物，可能引发炎症。从豚鼠分离的灌注气管从黏膜侧用1至100 μM的过氧亚硝酸根孵育15分钟。此后，在这些标本上构建组胺和乙酰甲胆碱的浓度-反应曲线。10 μM的过氧亚硝酸根引起显著的高反应性；对组胺和乙酰甲胆碱的最大收缩反应分别增强了30%和40%。在过氧亚硝酸根处理组中，检测到明显的上皮损伤以及嗜酸性粒细胞破坏。此外，气管内滴注100 nmol过氧亚硝酸根后3、5和10天，观察到麻醉动物对组胺的肺阻力显著升高。提示炎症过程中一氧化氮超氧阴离子自由基生成过氧亚硝酸根会诱导上皮损伤、介质释放，进而导致气道高反应性。这些发现可能具有临床意义，因为气道炎症、上皮损伤和高反应性是哮喘患者的特征性表现。
