Reperfusion liver injury induces down-regulation of eNOS and up-regulation of iNOS in lung tissues.
OBJECTIVE
Acute lung injury and inflammation can occur after hepatic ischemia/reperfusion (I/R). Little is known regarding the possible role of nitric oxide synthase expression in this complex type of lung injury.


METHODS
Real-time polymerase chain reactions and immunohistochemistry were used to assess the mRNA and protein expression of eNOS and iNOS in lung tissue after I/R challenge to the liver. Ischemia was induced by clamping the hepatic artery and portal vein for 40 minutes. After flow was restored, the liver was reperfused for 300 minutes. Blood samples were collected to assay three inflammatory parameters: tumor necrosis factor (TNF)-alpha, hydroxyl radicals, and NO. Lung lavage samples were assayed for protein and myeloperoxidase. The expression of eNOS and iNOS in lung tissues (n = 3) was also evaluated after I/R challenge to the liver. The iNOS inhibitor aminoguanidine was also tested in this I/R model.


RESULTS
Reperfusion of the liver produced increased blood concentrations of TNF, hydroxyl radicals, and NO (P < .001; n = 8). Bronchial lavage fluids showed higher levels of protein and myeloperoxidase in the I/R than in the sham-treated group (P < .01). eNOS expression was down-regulated and iNOS expression up-regulated in I/R lung tissues (n = 3). The iNOS inhibitor aminoguanidine (10 mg/kg) significantly attenuated the lung injury.


CONCLUSIONS
I/R injury to the liver induced lung injury involving systemic inflammatory responses and iNOS expression. Administration of aminoguanidine significantly attenuated the injury, suggesting that iNOS expression may play a critical role in lung injury induced by I/R of the liver.
Lin
H I
HI
Department of Medicine, Catholic Cardinal Tien Hospital, Taipei, Taiwan.
Chou
S J
SJ
Wang
D
D
Feng
N H
NH
Feng
E
E
Chen
C F
CF
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D017665:Hydroxyl Radical; D008102:Liver Circulation; D008168:Lung / Q000201:enzymology*; D008297:Male; D008760:Methylguanidine / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D008760:Methylguanidine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III