Morishita M, Sakamoto T, Ito K, Torii S
Department of Pediatrics, Nagoya University School of Medicine, Japan.
Eur J Pharmacol. 1996 Mar 7;298(2):149-54. doi: 10.1016/0014-2999(95)00793-8.
We investigated the role of activation of bradykinin receptors and mast cells in the microvascular leakage of the vessels of the skin induced by the intracutaneous (i.c.) injection of bradykinin in the rat. We evaluated the effects of HOE140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4H-benzo[4,5]cyclohepta[1, 2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell stabilizing properties, on the skin response. Evans blue dye extravasation served as an index of the increase in vascular permeability. Bradykinin (2-100 nmol/site i.c.) induced the extravasation of Evans blue dye in a dose-dependent manner. Ketotifen (20 mg/kg i.p.) significantly inhibited the leakage of dye induced by bradykinin (10 nmol/site i.c.) by 66.2%, while HOE140 (1 mg/kg i.v.) had no effect. The concomitant injection of HOE140 (0.2, 2 nmol/site) and bradykinin (10 nmol/site i.c.), also did not significantly reduce the extravasation of dye. We conclude that the extravasation of plasma induced by the i.c. injection of bradykinin is mediated mainly by stimulation of the skin mast cells, but not by bradykinin B2 receptors.
我们研究了缓激肽受体激活和肥大细胞在大鼠皮内注射缓激肽诱导的皮肤血管微血管渗漏中的作用。我们评估了缓激肽B2受体拮抗剂HOE140（D-精氨酸-[Hyp3,Thi5,D-Tic7,Oic8]缓激肽）和具有肥大细胞稳定特性的组胺H1受体拮抗剂酮替芬（4-(1-甲基-4-哌啶亚基)-4H-苯并[4,5]环庚[1,2-b]噻吩-10(9H)-酮富马酸氢盐）对皮肤反应的影响。伊文思蓝染料外渗作为血管通透性增加的指标。缓激肽（2 - 100 nmol/部位皮内注射）以剂量依赖性方式诱导伊文思蓝染料外渗。酮替芬（20 mg/kg腹腔注射）显著抑制缓激肽（10 nmol/部位皮内注射）诱导的染料渗漏达66.2%，而HOE140（1 mg/kg静脉注射）无作用。同时注射HOE140（0.2、2 nmol/部位）和缓激肽（10 nmol/部位皮内注射）也未显著减少染料外渗。我们得出结论，皮内注射缓激肽诱导的血浆外渗主要由皮肤肥大细胞的刺激介导，而非缓激肽B2受体。
