[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.
Hu
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DE
Department of Pharmacology, University of Cambridge.
Fan
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TP
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
D006454:Hemoglobins; D007375:Interleukin-1; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; C051090:bradykinin, Leu(8)-des-Arg(9)-; D001920:Bradykinin