[Leu8]des-Arg9-bradykinin inhibits the angiogenic effect of bradykinin and interleukin-1 in rats.

1. Subcutaneous implantation of sterile polyether sponges in rats elicited a reproducible neovascular response over 14 days, as determined by measurements of relative sponge blood flow by a 133Xe clearance technique. The angiogenic response was verified by quantitation of haemoglobin contents and histological evaluation of vascularized sponges. 2. Daily administration of 1 nmol of bradykinin (BK) into the implants significantly enhanced the basal sponge-induced neovascularization, leading to higher 133Xe clearance values, increased haemoglobin contents, cellularity and vascularity. 3. When given alone, lower doses of BK (10 pmol) or recombinant human interleukin-1 alpha (IL-1 alpha, 0.3 pmol) produced no apparent effects on the basal sponge-induced angiogenesis. However, co-administration of these two peptides produced an angiogenic response similar to that elicited by 1 nmol of BK. 4. The BK/IL-1 alpha-induced neovascularization was abolished by the bradykinin B1 receptor antagonist, [Leu8]des-Arg9-BK (1 nmol day-1), but not by the B2 receptor antagonist Ac-D-Arg-[Hyp3, D-Phe7, Leu8]-BK (1 nmol day-1). 5. Thus, if such interaction between BK and IL-1 alpha contributes to the excessive neovascularization in chronic inflammatory diseases, the blockade of B1 receptors may provide an effective treatment.