Markus Neef

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

Abstract 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 P P P P Conclusions : Urotensin II formation is upregulated in patients with cirrhosis and portal hypertension. The transhepatic gradient suggests a hepatic production of this peptide.

Acute haemodynamic effects of losartan in anaesthetized cirrhotic rats

Background  Portal hypertension in cirrhosis is the result of increased intrahepatic vascular resistance to portal outflow as well as increased portal tributary blood flow. The angiotensin II type 1 receptor antagonist losartan has been suggested as a portal pressure‐lowering drug in patients with cirrhosis.

Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock-out mice and is elevated in murine and human cirrhosis.

Abstract: 
Background: The role of endothelial nitric oxide synthase 3 (NOS‐3) in the hyperdynamic circulation associated with cirrhosis is established but not that of the neuronal (NOS‐1) isoform. We therefore investigated aortic NOS‐1 levels in NOS‐3 knock‐out (KO) and wildtype (WT) mice and in hepatic arteries of patients.

Vascular, hemodynamic and renal effects of low-dose losartan in rats with secondary biliary cirrhosis

Background: In cirrhosis, splanchnic and systemic vasodilatation induce a hyperdynamic circulatory dysfunction, portal hypertension and renal sodium retention. This vasodilatation is in part because of an impaired vascular response to α1‐adrenoceptor agonists. Recently, the angiotensin II type 1‐receptor antagonist losartan has been shown to attenuate portal hypertension. We hypothesized that losartan decreases portal pressure by counteracting the impaired vascular responsive to α1‐adrenoceptor agonists.

Portal hypertension is associated with increased mRNA levels of vasopressor G-protein-coupled receptors in human hepatic arteries

Background The contractile response of human splanchnic vessels to different vasoconstrictors is attenuated in cirrhosis. Functional studies indicate a cellular signalling defect upstream of the G‐protein level. The aim of the present study was to analyze expression and mRNA levels of the following most relevant vasopressor receptors in the smooth musculature of human hepatic arteries: α1 adrenoceptor (AR) subtypes a, b and d, angiotensin II type 1 receptor (AT1), arginine vasopressin receptor type 1a (V1a), endothelin receptor type A (ETA) and B (ETB).

Acenocoumarol is not a safe alternative for anticoagulation in phenprocoumon-induced hepatic failure. Report of two cases.

Acenocoumarol has been proposed repeatedly as a safe alternative drug regimen for oral anticoagulation in patients who have suffered phenprocoumon-induced fulminant hepatic failure. The current report describes 2 patients with phenprocoumon-induced hepatic failure, necessitating liver transplantation in 1 case, who showed recurrence of liver damage when oral anticoagulation with acenocoumarol was attempted. Thus, acenocoumarol may not be a safe therapeutic alternative for patients who survived severe phenprocoumon-induced hepatotoxicity.

Increased urotensin II plasma levels in patients with cirrhosis

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.