Generation and metabolism of angiotensins in the vascular wall.

血管壁中血管紧张素的生成和代谢。

基本信息

批准号：
61570436
负责人：
IKEDA Masaharu
金额：
$ 1.41万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570436/
关键词：
後肢潅流アンジオテンシンI アンジオテンシンII アンジオテンシン変換酵素血管壁レニンアンジオテンシン系下肢(後肢)還流アンジオテンシン【I】アンジオテンシン【II】血管壁レニン血管壁アンジオテンシン変換酵素

项目摘要

The renin-angiotensin-aldosterone system has been known as one of the most potent controlling system of the blood pressure. The circulating renin-angiotensin system has been thought to be the main source of angiotensins. However, recently there are several reports that the major sites of the formation of angiotensin are peripheral tissues including brain,kidney,adrenal gland,and arterial wall. Full sets of the renin-angiotensin system, i.e.,renin, converting enzyme and renin substrate are reported to exist in those tissues.The purpose of the study was to demonstrate the generation and metabolism of angiotensins using the hindquarter vascular perfusion system and to clarify whether there exists the alternate pathway of angiotensin formation in addition to the classical renin-converting enzyme cascade. Following results were obtained;(1)Hindquarter perfusion system was establishid.(2)Synthetic angiotensin II(10(micrn)g/20ml) was perfused in the perfusing system and angiotensin II was extracted from the perfusate and about 20 % of angiotensin II was recovered.(3)When angiotensin I(100 ng/20 ml) was perfused in the system, about 20 % of angiotensin II was generated. Formation of angiot ensin II was partially inhibited by captopril,a potent converting enzyme inhibitor and more strongly inhibited by captopril plus trasylol,a trypsin-kallikrein inhibitor.(4)When synthetic tridecapeptide renin substrate(10(micrn)g/20 ml) was perfused,angiotensin I and II were recovered from the perfusate. Although captopril could not inhibit the generation of angiotensin II.(5)To check whether the immunoreactive angiotensin II is the octapeptide angiotensin II was also conducted after high performance liquid chromatography.From these results,the vasculature per se plays roles to generate and metabolize angiotensins. In addition, these results also suggest that some enzymes other thana classical reninconverting enzyme system might perticipate in thegeneration or conversion of angiotensins.

肾素-血管紧张素-醛固酮系统被认为是最有效的血压控制系统之一。循环肾素-血管紧张素系统被认为是血管紧张素的主要来源。然而，最近有报道称，血管紧张素的主要形成部位是周围组织，包括脑、肾、肾上腺和动脉壁。据报道，这些组织中存在全套肾素-血管紧张素系统，即肾素、转化酶和肾素底物。本研究的目的是利用后躯血管灌注系统证明血管紧张素的生成和代谢，并阐明是否除了经典的肾素转化酶级联之外，还存在血管紧张素形成的替代途径。得到如下结果：(1)建立后躯灌注系统。(2)灌注系统中灌注合成血管紧张素II(10μg/20ml)，从灌注液中提取血管紧张素II，约占血管紧张素II的20％。 (3)当系统中灌注血管紧张素I(100ng/20ml)时，约20%生成血管紧张素II。血管紧张素 II 的形成被卡托普利（一种有效的转化酶抑制剂）部分抑制，并且被卡托普利加曲塞洛（一种胰蛋白酶激肽释放酶抑制剂）更强地抑制。(4)当合成的十三肽肾素底物（10（微米）g/20 ml）为灌注后，从灌注液中回收血管紧张素I和II。虽然卡托普利不能抑制血管紧张素II的生成。(5)也通过高效液相色谱法检查免疫反应性血管紧张素II是否是八肽血管紧张素II。从这些结果来看，脉管系统本身起着血管紧张素生成和代谢的作用。。此外，这些结果还表明，除了经典的肾素转化酶系统之外的一些酶可能参与血管紧张素的生成或转化。