[Peroxynitrite mediated acute lung injury induced by lipopolysaccharides in rats]

To explore the roles of peroxynitrite (ONOO(-)) in acute lung injury induced by lipopolysaccharides (LPS).

Nitrotyrosine (NT), a specific marker of in vivo ONOO(-) production, was detected with immunohistochemical technique in rat lung during endotoxin shock (LPS 5 mg/kg iv). Lung coefficient (LC), lung wet/dry weight ratio (W/D), the contents of water and Evans blue (EB) in lungs were measured after intratracheal insufflation of ONOO(-) with different doses. Monastral blue (MB)-labelled blood vessels and pathological changes in lungs were examined under a light microscope.

After 2 or 6 hours of LPS intravenous administration, severe lung injury and positive signals of NT occurred with the latter located in the pulmonary macrophages, endothelia, subendothelial and muscular layers of the pulmonary artery. Administration of exogenous ONOO(-) caused dose-dependent increase in LC, W/D, ater and EB contents and in the number of MB-labelled blood vessels in rat lungs, together with significant pathological alterations such as diffuse alveolar collapse, capillary congestion in the septa and focal hemorrhage.

In the early stage of endotoxin shock, severe lung injury and ONOO(-) production simultaneously exist, and exogenous ONOO(-) could induce significant dysfunction of microvascular endothelial barrier and lung injury, indicating that ONOO(-) generation in vivo may be involved in the pathogenesis of acute lung injury.