Generation and metabolism of angiotensins in the vascular wall.

肾素-血管紧张素-醛固酮系统被认为是控制血压最有效的系统之一。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，最近有几篇报道称血管紧张素的主要形成部位是外周组织，包括脑、肾、肾上腺和动脉壁。整套肾素-血管紧张素系统，即肾素、转化酶和肾素底物据报道存在于这些组织中。本研究的目的是通过后段血管灌注系统证明血管紧张素的生成和代谢，并阐明除了经典的肾素转换酶级联外，是否存在血管紧张素形成的替代途径。得到以下结果：(1)建立后肢灌注系统。(2)在灌注系统中灌注合成血管紧张素II(10(micrn)g/20ml)，从灌注液中提取血管紧张素II，回收约20%的血管紧张素II。(3)系统灌注血管紧张素I（100ng / 20ml）时，生成约20%的血管紧张素II。卡托普利（一种有效的转化酶抑制剂）部分抑制血管生长素II的形成，而卡托普利加trasylol（一种胰蛋白酶-钾likrein抑制剂）更强烈地抑制血管生长素II的形成。(4)灌注合成三肽肾素底物（10(micrn)g/20 ml）后，从灌注物中回收血管紧张素I和II。虽然卡托普利不能抑制血管紧张素II的生成。(5)采用高效液相色谱法检测免疫反应性血管紧张素II是否为八肽血管紧张素II。从这些结果来看，血管系统本身在产生和代谢血管紧张素方面起作用。此外，这些结果还表明，除经典肾素转换酶系统外，其他一些酶可能参与血管紧张素的生成或转化。

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.