Proangiogenic Effect of Angiotensin-Converting Enzyme Inhibition Is Mediated by the Bradykinin B2 Receptor Pathway

Recent studies have suggested a proangiogenic effect of angiotensin-converting enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE inhibition may be mediated, in part, by bradykinin (BK) B2-receptor pathway. This study therefore examined the neovascularization induced by ACE inhibitor treatment in B2 receptor–deficient mice (B2) in a model of surgically induced hindlimb ischemia. After artery femoral occlusion, wild-type and B2 mice were treated with or without ACE inhibitor (perindopril, 3 mg/kg/d) for 28 days. Angiogenesis was then quantitated by microangiography, capillary density measurement, and laser Doppler perfusion imaging. The protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were determined by Western blot. In wild-type animals, vessel density and capillary number in the ischemic leg were raised by 1.8- and 1.4-fold, respectively, in mice treated with ACE inhibitor when compared with the nontreated animals (P