The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat

• DOI: 10.1002/hep.20244
• Publication Date: 2004-05-27T20:02:01Z
• Authors: Yiqun Ling; Junlan Zhang; Bao Luo; Daisheng Song; Lichuan Liu; Liping Tang; Cecil R. Stockard; William E. Grizzle; David D. Ku; Michael B. Fallon
• Keywords: Hepatopulmonary syndrome; Ambrisentan

Endothelin-1 (ET-1) stimulation of endothelial nitric oxide synthase (eNOS) via pulmonary endothelin B (ET ) receptors and intravascular macrophage accumulation with expression inducible (iNOS) heme oxygenase-1 (HO-1) are implicated in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Our aim was to evaluate the role ET-1 development HPS. The time course molecular physiological changes HPS effects selective receptor antagonists vivo were assessed CBDL. Effects on intralobar vascular segment reactivity eNOS activity rat microvascular cells (RPMVECs) also evaluated. Hepatic plasma levels increased 1 week CBDL association a subsequent increase ET onset Selective inhibition significantly decreased ameliorated artery segments had markedly mediated, dependent vasodilatory responses compared controls triggered an RPMVECs. Pulmonary macrophages accumulated expressed HO-1 iNOS at 3 weeks. blockade production. In conclusion , plays central modulating micovascular tone (Hepatology 2004;39:1593-1602.)