title: Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomediques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. mercefernandez@ub.es
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernandez
authors.forename: Marc
authors.initials: M
authors.lastname: Mejias
authors.forename: Bernhard
authors.initials: B
authors.lastname: Angermayr
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Garcia-Pagan
authors.forename: Juan
authors.initials: J
authors.lastname: Rodés
authors.forename: Jaime
authors.initials: J
authors.lastname: Bosch
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D003097:Collateral Circulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000150:complications* / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000187:drug effects; D011168:Portal System / Q000503:physiopathology*; D011169:Portal Vein / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C116890:Semaxinib; D040301:Vascular Endothelial Growth Factor Receptor-2