Intake of red wine polyphenols prevents the stimulatory effect of angiotensin II on ischemia-induced neovascularization in the rat hindlimb

Angiogenesis plays a key role in the development of atherosclerotic lesions. Epidemiological studies have indicated that regular intake of red wine is associated with a reduced risk of coronary diseases. This study examined whether intake of red wine polyphenols (RWPs) affects the ischemia-induced formation of new blood vessels and its potentiation by infusion of a non-hypertensive dose of angiotensin II (Ang II, 0.1 mg/kg/day), in the rat hindlimb. Ang II infusion using osmotic minipumps potentiated the ischemia-induced neovascularizaton as assessed by microangiography and the number of capillaries in the hindlimb. This effect was associated with an increased formation of reactive oxygen species as assessed with dihydroethidine, expression of endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-2 (HIF-2), and protein nitration as assessed by immunofluorescence and Western blotting. RWPs did not affect hemodynamic parameters but prevented the Ang II-induced neovascularization, expression of eNOS, VEGF and HIF-2 and protein nitration. Intake of RWPs alone was without effect. The present findings indicate that RWPs prevent the stimulatory effect of Ang II on ischemia-induced neovascularization most likely by preventing oxidative stress and the expression of pro-angiogenic factors including VEGF, eNOS and HIF-2