[LEU(8)]DES-ARG(9)-BRADYKININ INHIBITS THE ANGIOGENIC EFFECT OF BRADYKININ AND INTERLEUKIN-1 IN RATS

被引:66
作者
HU, DE [1 ]
FAN, TPD [1 ]
机构
[1] UNIV CAMBRIDGE, DEPT PHARMACOL, TENNIS COURT RD, CAMBRIDGE CB2 1QJ, ENGLAND
基金
英国惠康基金;
关键词
ANGIOGENESIS; BRADYKININ; INTERLEUKIN-1; ANGIOSUPPRESSION; B(1)-RECEPTOR AND B(2)-RECEPTOR ANTAGONISTS;
D O I
10.1111/j.1476-5381.1993.tb13525.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Xe-133 clearance technique. The angiogenic response was verified by quantitation of haemoglobin contents and histological evaluation of vascularized sponges. Daily administration of 1 nmol of bradykinin (BK) into the implants significantly enhanced the basal sponge-induced neovascularization, leading to higher Xe-133 clearance values, increased haemoglobin contents, cellularity and vascularity. When given alone, lower doses of BK (10 pmol) or recombinant human interleukin-1 alpha (IL-1alpha 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. The BK/IL-1alpha-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). Thus, if such interaction between BK and IL-1alpha contributes to the excessive neovascularization in chronic inflammatory diseases, the blockade of B1 receptors may provide an effective treatment.
引用
收藏
页码:14 / 17
页数:4
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