The bradykinin/B1 receptor promotes angiogenesis by up‐regulation of endogenous FGF‐2 in endothelium via the nitric oxide synthase pathway

Abstract

SPECIFIC AIMSIn this study we addressed the hypothesis that the contribution of bradykinin (BK) to angiogenesis depends on the type of receptor activated in endothelium and the ability to trigger an autocrine loop via the nitric oxide synthase (NOS) pathway. By the use of selective agonists and antagonists for the B1 and the B2 receptor, the effect of the kinin was assessed in vivo in the rabbit cornea, and the signaling cascades downstream receptor activation have been investigated on microvascular endothelial cells.PRINCIPAL FINDINGS1. The bradykinin/B1 receptor promotes angiogenesis in the rabbit corneaGradient dismission of nanomolar concentration of BK (1 μg/pellet) into the cornea of albino rabbits induced a strong angiogenic response in the absence of an inflammatory reaction. The B1 receptor agonist Lys-des-Arg9-BK reproduced BK effect (Fig. 1a⤻ , b⤻ ), whereas the B2 receptor agonist kallidin failed unless higher doses of the peptide were used and inflammatory cells were recruited into the cornea...