Endothelin-1 in the rat bile duct ligation model of hepatopulmonary syndrome: correlation with pulmonary dysfunction.
OBJECTIVE
Models of hepatopulmonary syndrome require both hepatic injury and portal hypertension to develop pulmonary microvascular and gas exchange abnormalities. Recently, increased endothelin-1 levels associated with vasodilatation, have been observed in cirrhosis. We investigated endothelin-1 production in common bile duct ligated animals with hepatopulmonary syndrome in comparison to partial portal vein ligated animals that do not develop hepatopulmonary syndrome.


METHODS
Organ and plasma endothelin-1 were measured in sham, bile duct ligated and portal vein ligated rats, and Northern analysis and immunohistochemistry were performed in liver. Plasma endothelin-1 levels were correlated with pulmonary endothelial nitric oxide synthase levels and alveolar-arterial oxygen gradients.


RESULTS
Hepatic and plasma endothelin-1 increased only after bile duct ligation, and were accompanied by increased hepatic endothelin-1 mRNA and increased endothelin-1 protein in biliary epithelium. Plasma endothelin-1 levels correlated directly with both pulmonary endothelial nitric oxide synthase levels and alveolar-arterial gradients.


CONCLUSIONS
Enhanced hepatic production and increased plasma levels of endothelin-1 occur after bile duct ligation, but not after portal vein ligation, and correlate with associated molecular and gas exchange alterations in the lung. Endothelin-1 may contribute to the pathogenesis of hepatopulmonary syndrome.
Luo
B
B
Department of Internal Medicine and Liver Center, University of Alabama at Birmingham, 35294-0007, USA.
Abrams
G A
GA
Fallon
M B
MB
D000818:Animals; D001652:Bile Ducts; D019332:Endothelin-1 / Q000032:analysis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D020065:Hepatopulmonary Syndrome / Q000209:etiology* / Q000503:physiopathology; D008026:Ligation; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011169:Portal Vein; D011659:Pulmonary Gas Exchange; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat