Differential contribution of bradykinin receptors in angiogenesis

Bradykinin (BK) contributes to the inflammatory response inducing vasodilation of postcapillary venules and has been demonstrated to induce neovascular growth in subcutaneous rat sponges. In this study the ability of BK to stimulate cell growth and migration in cultured endothelium from coronary postcapillary venules (CVEC) has been investigated. BK promotes growth of endothelial cells and its mitogenic activity involves c-Fos expression. Only the B1 receptor appears to be responsible for the proliferation induced by BK and suggests that this type of receptor might be implicated in favouring angiogenesis of coronary venules, Phospholipase C (PLC) activation and the endogenous upregulation of nitric oxide synthase (NOS) were monitored in response to B1 and B2 receptor activation. BK-induced IP turnover was triggered by B2 activation, while NOS activation was linked to the B1 receptor. NOS inhibition in CVEC prevented BK/B1 induced cell growth. These results substantiate the protective and trophic role of BK on microvascular endothelium by demonstrating that B1 receptor stimulation on venular endothelium is mandatory for the angiogenic effect of BK through its coupling to NOS activation