Bradykinin B1 receptor induces the proliferation of coronary venular endothelium and potentiates FGF-2 effect

Bradykinin (BK) has been demonstrated to induce neovascular growth in subcutaneous rat sponges. To clarify the role of BK in angiogenesis, we have evaluated the effect of BK on the growth and mobilization of endothelial cells isolated from coronary postcapillary venules (CVEC). BK induced a concentration-dependent proliferation of subconfluent and synchronized CVEC. Maximal effect was produced by 0.1 μM concentration inducing cell growth by 50%. The selective B1 receptor agonist Des-Arg9-BK mimicked the proliferative effect of BK, while the B2 receptor agonist kallidin was devoid of any activity. When BK was tested on endothelial cell migration neither the natural peptide or the selective agonists exerted any effect. The proliferation induced by BK was abolished in a concentration-dependent manner by the addition of the B1 selective antagonist Des-Arg9-Leu8-BK. BK and Des-Arg9-BK potentiated the growth promoting effect of a threshold concentration of fibroblast growth factor-2 (FGF-2). Our results indicate that BK-B1 receptor affects angiogenesis by promoting the endothelium from postcapillary venules to undergo mitosis but not migration. The synergistic effect of BK with FGF-2 suggest that molecules present at tissue level are able to improve myocardial recovery after ischemia by favouring angiogenesis of coronary venules.