Increased urotensin II plasma levels in patients with cirrhosis and portal hypertension

BACKGROUND/AIMS: Vasodilatation--despite activation of endogenous vasoconstrictors--is pronounced in portal hypertension. We therefore investigated the role of Urotensin II (U II), a newly described peptide reported to be a vasoconstrictor in the central arterial compartment and a vasodilator in the splanchnic vasculature. METHODS: U II immunoreactivity was measured in 50 patients with cirrhosis and in 15 healthy controls. U II levels were compared in portal venous and central venous blood of 30 patients immediately before transjugular intrahepatic porto-systemic stent shunt implantation. RESULTS: U II levels (median, range, ng/ml) were significantly increased in cirrhotics (12.3, 1.6-41.4) compared to controls (3.6, 0.1-12.0; P<0.001). In patients with cirrhosis, U II levels were significantly higher in central venous (12.9, 2.5-41.4) than in portal venous blood (11.0, 0.6-31.9; P<0.005). U II levels were higher in ascitic than in non-ascitic patients (P<0.02). They correlated positively with the wedged hepatic venous pressure gradient (rho=0.34, P<0.005) and negatively with the mean arterial pressure (rho=-0.41; P<0.001). CONCLUSIONS: Urotensin II formation is upregulated in patients with cirrhosis and portal hypertension. The transhepatic gradient suggests a hepatic production of this peptide.