Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats†

• DOI: 10.1002/hep.22170
• Publication Date: 2008-02-07T15:21:05Z
• Authors: Jonel Trebicka; Ludger Leifeld; Martin Hennenberg; Erwin Biecker; Andreas Eckhardt; Nicolas Fischer; Andrea Schulze Pr...; Christoph Clemens; Frank Lammert; Tilman Sauerbruch; Jörg Heller
• Keywords: Hyperdynamic circulation; Mean arterial pressure

In cirrhosis, splanchnic vasodilation contributes to portal hypertension, subsequent renal sodium retention, and formation of ascites. Urotensin II(U-II) is a constrictor large conductive vessels. Conversely, it relaxes mesenteric vessels, decreases glomerular filtration, increases retention. patients with U-II plasma levels are increased. Thus, we investigated hemodynamic effects its receptor antagonist, palosuran, in cirrhotic bile duct-ligated rats (BDL). BDL sham-operated rats, studied acute (3 nmol/kg; intravenously) palosuran (10 mg/kg; oral administration (30 mg/kg/day; 3 days) on hemodynamics function. We localized U-II-receptor (UTR) livers veins by immunostaining. determined U-II-plasma enzyme-linked immunosorbent assay (ELISA), nitrite/nitrate-levels Griess-reaction. RhoA/Rho-kinase endothelial nitric oxide synthase (eNOS) pathways were western blot analysis reverse transcription polymerase chain reaction (RT-PCR) arteries. levels, as well UTR-receptor expression significantly further augmented the increased pressure (PP) decreased mean arterial (MAP), whereas PP without affecting MAP. The decrease was associated an increase vascular resistance. treatment up-regulated RhoA Rho-kinase, Rho-kinase-activity, diminished (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling. Moreover, blood flow, sodium, water excretion rats.In mediator vasodilation, hypertension antagonist might represent new therapeutic option liver cirrhosis hypertension.