Inhibition of Phosphodiesterase 5 -a Novel Therapeutic Strategy for Portal Hypertension L. Halverscheid 1 , P. Deibert 2 , B. Pannen 1 , R. Schmidt 2 , M. Roessle 2 , W. Kreisel 2 1 University Hospital Duesseldorf, Germany, 2 University Hospital Freiburg, Germany Introduction: The NO-cyclic GMP system is a key factor in the regulation of splanchnic and hepatic blood flow and may be a target for medical treatment of portal hypertension. Clinical data have shown that inhibitors of phosphodiesterase 5 (PDE5) lower portal pressure in cirrhotics. Methods: We monitored in rats the effects of the PDE5 inhibitors vardenafil and sildenafil on systemic and hepatic hemodynamic parameters up to 60 minutes after the drug. The drugs were administered intravenously into the tail vein at 1 (group A), 10 (group B), and 100 g/kg body weight (group C). 0.9% NaCl was the control. N = 7 for each group. Results: The most prominent changes were observed in the vardenafil B group: Mean arterial and portal venous pressure decreased (-9%, -8%), as well as portal venous, hepatic arterial, and systemic vascular resistance (-31%, -30%, -12%). Portal venous and sinusoidal flow increased (+31%, +13%). In the vardenafil C and sildenafil B and C groups there was an increase of portal venous flow by 20-30%, an increase of sinusoidal flow by 12-30%, and a decrease of portal venous resistance by about 25%. There was a trend for reduction of portal venous pressure. Conclusions: Vardenafil and sildenafil influence portal hemodynamics in the rat. Portal venous flow increases by 20-30%, portal venous resistance decreases by >25%. Dependent on the dose, portal venous pressure decreases significantly. These data yield further evidence that PDE5 inhibitors may be a novel therapeutic option for portal hypertension.