Role of nitric oxide and peroxynitrite anion in lung injury induced by intestinal ischemia-reperfusion in rats.
OBJECTIVE
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 (NO(2)(-)/NO(3)(-)) contents and morphological changes were examined. Western blot was used to detect the iNOS 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 NO(2)(-)/NO(3)(-) 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 iNOS and NT were also increased in the lung. Compared with IR group, the contents of MDA and NO(2)(-)/NO(3)(-) 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 NT staining was also decreased.


CONCLUSIONS
Intestinal IR increases NO and ONOO(-) production in the lung, which may be involved in intestinal IR-mediated lung injury.
Zhou
Jun-Lin
JL
Department of Hand Surgery, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China. zhjunlin@yahoo.com
Jin
Guo-Hua
GH
Yi
Yi-Ling
YL
Zhang
Jun-Lan
JL
Huang
Xin-Li
XL
D000818:Animals; D000838:Anions / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000838:Anions; D009566:Nitrates; D009573:Nitrites; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat