Sardi S P, Pérez H, Antúnez P, Rothlin R P
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Eur J Pharmacol. 1997 Feb 19;321(1):33-8. doi: 10.1016/s0014-2999(96)00927-2.
The present study was undertaken to demonstrate the presence of bradykinin B1 receptors mediating contraction of human umbilical vein. The bradykinin B1 receptor selective agonist, des-Arg9-bradykinin, produced a dose-dependent contractile response of human umbilical vein rings. Furthermore, des-Arga-bradykinin-mediated response increased in a time-dependent manner in vitro. The maximal response to des-Arg9-bradykinin, expressed as percentage of the maximum elicited by serotonin, was: 10 +/- 2 at 15 min, 55 +/- 5 at 120 min and 80 +/- 3 at 300 min. Des-Arg9-bradykinin-mediated contractions were inhibited by the specific bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin which produced parallel shifts in the dose-response curve to the selective bradykinin B1 receptor agonist. Schild regression analysis of data established a pA2 value of 6.16 +/- 0.06. Kinin-induced contraction was not modified by pre-treatment with indomethacin (10 microM), a cyclo-oxygenase inhibitor. On the other hand, continuous exposure to the anti-inflammatory steroid dexamethasone (100 microM) or to the protein synthesis inhibitor cycloheximide (70 microM) largely prevented the sensitization to des-Arg9-bradykinin in incubated human umbilical vein rings. These results confirm the presence of bradykinin B1 receptors which mediate contraction in isolated human umbilical vein. These responses are up-regulated in a time- and protein synthesis-dependent process.
本研究旨在证明缓激肽B1受体介导人脐静脉收缩的存在。缓激肽B1受体选择性激动剂去精氨酸9-缓激肽对人脐静脉环产生剂量依赖性收缩反应。此外，去精氨酸9-缓激肽介导的反应在体外呈时间依赖性增加。以血清素引起的最大反应百分比表示，去精氨酸9-缓激肽的最大反应为：15分钟时为10±2，120分钟时为55±5，300分钟时为80±3。去精氨酸9-缓激肽介导的收缩被特异性缓激肽B1受体拮抗剂去精氨酸9-[亮氨酸8]缓激肽抑制，该拮抗剂使对选择性缓激肽B1受体激动剂的剂量反应曲线平行移动。对数据进行Schild回归分析得出pA2值为6.16±0.06。用环氧化酶抑制剂吲哚美辛（10微摩尔）预处理未改变激肽诱导的收缩。另一方面，持续暴露于抗炎类固醇地塞米松（100微摩尔）或蛋白质合成抑制剂环己酰亚胺（70微摩尔）在很大程度上阻止了孵育的人脐静脉环对去精氨酸9-缓激肽的致敏。这些结果证实了缓激肽B1受体的存在，其介导分离的人脐静脉收缩。这些反应在时间和蛋白质合成依赖性过程中上调。
