Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats

Background/Aims: Portal hypertension is characterized by the development of a hyperdynamic splanchnic circulation. To determine whether this process is angiogenesis-dependent, we assessed the effects of SU5416, a specific inhibitor of VEGF receptor-2, in portal hypertensive rats. Methods: Rats with portal hypertension induced by partial portal vein ligation were treated with SU5416 or vehicle during 5 days. Then, hemodynamic studies were performed using radioactive microspheres. Protein expressions of CD31, VEGF receptor-2 and VEGF were also determined by Western blotting. Results: Treatment of portal hypertensive rats with SU5416 resulted in a significant and marked decrease (by 44%) in portal venous inflow, and increases in splanchnic arteriolar resistance (by 68%) and portal venous resistance (by 93%). In addition, SU5416 administration significantly inhibited the formation of portal-systemic collateral vessels (52% inhibition), as well as the splanchnic CD31 and VEGF receptor-2 protein expressions in portal hypertensive rats, compared with those receiving vehicle. Conclusions: This study demonstrates that the development of hyperdynamic splanchnic circulation and the formation of portal-systemic collateral vessels in portal hypertensive rats are angiogenesis-dependent processes that can be markedly inhibited by blockade of the VEGF signaling pathway. Therefore, modulation of angiogenesis may represent a potential target in the treatment of portal hypertension. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.