B1 RECEPTOR INVOLVEMENT IN THE EFFECT OF BRADYKININ ON VENULAR ENDOTHELIAL-CELL PROLIFERATION AND POTENTIATION OF FGF-2 EFFECTS

1 Bradykinin (BK) contributes to the inflammatory response inducing va sodilation of postcapillary venules and has been demonstrated to induc e neovascular growth in subcutaneous rat sponges. 2 In this study the ability of BK to stimulate cell growth and migration in cultured endot helium from coronary postcapillary venules (CVEC) has been investigate d. 3 [H-3]-thymidine incorporation in subconfluent and synchronised CV EC was used to monitor DNA synthesis over 24 h. BK promoted a concentr ation-dependent increase of DNA synthesis with maximal activity at 100 nM. At this concentration BK also induced 18 fold accumulation of c-F os protein immunoreactivity in the nucleus within 1 h from peptide exp osure. 4 The total number of cells recovered after 48 h exposure to BK was increased in a concentration-dependent manner. Maximal effect was produced by 100 nM concentration of the peptide which produced 50% in crease in cell number. The selective B1 receptor agonist Des-Arg9-BK m imicked the proliferative effect of BK, while the B2 receptor agonist kallidin was devoid of any activity. The proliferation induced by BK w as abolished in a concentration-dependent manner by the addition of th e B1 selective antagonist Des-Arg9-Leu8-BK, while the selective B2 rec eptor antagonist HOE140 did not modify BK-induced growth. 5 DNA synthe sis and growth promoted by a threshold concentration of fibroblast gro wth factor-2 (FGF-2) (0.25 nM) were potentiated by increasing concentr ations of BK and Des-Arg9-BK. 6 Endothelial cell migration assessed by the Boyden Chamber procedure was not promoted by BK or the selective B1 and B2 receptor agonists. 7 These data are the first demonstration that BK promotes growth of endothelial cells from postcapillary venule s. The mitogenic activity of BK involves c-Fos expression and potentia tes the growth promoting effect of FGF-2. Only the B1 receptor appears to be responsible for the proliferation induced by BK and suggests th at this type of receptor might be implicated in favouring angiogenesis of coronary venules.