Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome

• Published in: Journal of hepatology 2003-05, Vol.38 (5), p.556-563
• Main Authors: Luo, Bao, Liu, Lichuan, Tang, Liping, Zhang, Junlan, Stockard, Cecil R, Grizzle, William E, Fallon, Michael B
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cirrhosis; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Common Bile Duct; Common bile duct ligation; Endothelial nitric oxide synthase; Endothelin receptor; Endothelin-1; Endothelin-1 - metabolism; Endothelium, Vascular - metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Hepatopulmonary syndrome; Hepatopulmonary Syndrome - metabolism; Hepatopulmonary Syndrome - physiopathology; Hypertension, Portal - metabolism; Hypertension, Portal - physiopathology; Intrapulmonary vasodilatation; Ligation; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; Other diseases. Semiology; Portal hypertension; Portal Vein; Portal vein ligation; Pulmonary artery; Pulmonary Artery - physiology; Pulmonary Circulation; Rats; Rats, Sprague-Dawley; Receptor, Endothelin B - genetics; Receptor, Endothelin B - metabolism
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(03)00012-6

Background/Aims: In experimental hepatopulmonary syndrome (HPS), hepatic endothelin-1 (ET-1) release during common bile duct ligation (CBDL) and ET-1 infusion in pre-hepatic portal hypertension after portal vein ligation (PVL) initiate vasodilatation through an endothelin B receptor mediated increase in pulmonary endothelial nitric oxide synthase (eNOS). We evaluated if pulmonary ET receptor expression changes in experimental cirrhosis and portal hypertension and confers susceptibility to HPS. Methods: In normal, PVL and CBDL animals, lung ET receptor expression and localization were assessed and ET receptor levels and functional analysis of ET-1 effects on eNOS levels were evaluated in intralobar pulmonary artery (PA) and aortic (AO) segments. Normal rats underwent evaluation for HPS after ET-1 infusion. Results: There was a selective increase in ET B receptor expression in the pulmonary vasculature from PVL and CBDL animals. ET-1 stimulated NO production and an ET B receptor mediated increase in eNOS levels in PA segments from PVL and CBDL animals, but not normal animals. ET-1 did not alter lung eNOS levels or cause HPS in normal rats. Conclusions: ET B receptor expression and ET-1 mediated eNOS and NO production are enhanced in the lung vasculature in cirrhotic and portal hypertensive animals and correlate with in vivo susceptibility to ET-1 mediated HPS.