Inhibition of hydrogen peroxide prevents the development of VEGF‐induced angiogenesis in portal hypertensive rats

Abstract

AimsTo determine specific effects of inhibiting hydrogen peroxide (H2O2) on splanchnic hemodynamics and angiogenesis in portal hypertension of rats.Methods: Portal hypertensive models were induced by partial portal vein ligation (PPVL). The rats then, received either polyethylene glycol‐catalase (H2O2 inhibitor; PPVL‐PEG) or vehicle (PPVL‐Veh) for 8 days. The hemodynamic studies were performed using colored microsphere technique. Intestinal expressions of VEGF/VEGF‐2 and CD31 (angiogenesis markers) was determined by western blotting, and levels of H2O2 were measured by the Hydrogen Peroxide Assay Kit.Results: Portal pressure was significantly higher, associated with lower splanchnic arteriolar resistance in PPVL group (14.4±0.9 and 11.2±1.1mmHg) than those of normal rats (6.1±0.4 and 35.1±4.0 mmHg). Upregulation of VEGF/VEGF‐2 and CD31 in the intestine/mesentery of PPVL group was indicative of angiogenesis, which consequentially, initiated great collateral vessel formation, leading to the development of splanchnic hyperdynamic circulation. Moreover, levels of H2O2 in the intestine and mesentery of PPVL group of rats were significantly higher than those of normal rats. These alterations were significantly alleviated after treatment of portal hypertensive rats with PEG‐catalase, suggesting a key role of H2O2 in the responses.ConclusionsH2O2 plays an important role in the pathogenesis of portal hypertension, characterized as the potentiation of splanchnic neovascularisation and development of splanchnic hyperdynamic circulation.