Role of nitric oxide and peroxynitrite anion in lung injury induced by intestinal ischemia-reperfusion in rats

AIM: To evaluate effects of nitric oxide (NO) and peroxynitrite anion (ONOO-) on lung injury following intestinal ischemia-reperfusion (IR) in rats. METHODS: A rat model of intestinal ischemia was made by clamping superior mesenteric artery and lung injury was resulted from reperfusion. The animals were randomly divided into 3 groups: sham operation (Sham), 2 h ischemia followed by 2 h reperfusion (IR) and IR pretreated with aminoguanidine (AG) - an inhibitor of inducible NO synthase (iNOS) 15 minutes before reperfusion (IR+AG). The lung malondialdehyde (MDA) and nitrate/nitrite (NO2-/NO3-) contents and morphological changes were examined. Western blot was used to detect the NOS protein expression. Immunohistochemical staining was used to determine the change of nitrotyrosine (NT)- a specific footprint of ONOO-. RESULTS: The morphology revealed evidence for lung edema, hemorrhage and polymorphonuclear sequestration after intestinal IR. Compared with sham group, lung contents of MDA and NO2-/NO3- in IR group were significantly increased (12.00 +/- 2.18 vs 23.44 +/- 1.25 and 76.39 +/- 6.08 vs 140.40 +/- 4.34, P < 0.01) and the positive signals of NOS and NT were also increased in the lung. Compared with IR group, the contents of MDA and NO2-/NO3- in IR+AG group were significantly decreased (23.44 +/- 1.25 vs 14.66 +/- 1.66 and 140.40 +/- 4.34 vs 80.00 +/- 8.56, P < 0.01) and NIT staining was also decreased. CONCLUSION: Intestinal IR increases NO and ONOO- production in the lung, which may be involved in intestinal IR-mediated lung injury.