Mizuno K, Nakamaru M, Higashimori K, Inagami T
Department of Biochemistry and Hypertension, Specialized Center of Research (SCOR), Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Hypertension. 1988 Mar;11(3):223-9. doi: 10.1161/01.hyp.11.3.223.
Isolated rat hindlegs were perfused with Krebs-Ringer solution, and immunoreactive angiotensin II (irAng II) released into the perfusate was directly determined using a Sep-Pak C18 cartridge connected to the perfusion system. High performance liquid chromatography clearly demonstrated the presence of angiotensin I (Ang I), angiotensin II (Ang II), and a small amount of angiotensin III. The spontaneous release of irAng II was as high as about 600 pg/30 min, which was stable up to 3 hours. Captopril added to the perfusion medium (10(-9) to 10(-6) M) suppressed irAng II release in a dose-dependent manner (p less than 0.001), and it (10(-6)M) caused a reciprocal increase of irAng I release (p less than 0.05). Oral pretreatment of captopril (50 mg/kg/day) for 1 week suppressed the irAng II release by 31% (p less than 0.02). The same treatment with SA 446, a highly lipophilic angiotensin converting enzyme inhibitor, inhibited the irAng II release by 63% (p less than 0.001). On the other hand, the two inhibitors suppressed the plasma irAng II to very similar extents. Pretreatment with SA 446 plus nephrectomy did not cause any further change in irAng II release as compared with that with SA 446 alone. These results provide direct proof for local generation and subsequent secretion of Ang II by peripheral vascular tissue.
将分离的大鼠后肢用 Krebs-Ringer 溶液灌注，使用连接到灌注系统的 Sep-Pak C18 柱直接测定释放到灌注液中的免疫反应性血管紧张素 II（irAng II）。高效液相色谱法清楚地证明了血管紧张素 I（Ang I）、血管紧张素 II（Ang II）和少量血管紧张素 III 的存在。irAng II 的自发释放高达约 600 pg/30 分钟，在长达 3 小时内保持稳定。添加到灌注培养基中的卡托普利（10^(-9) 至 10^(-6) M）以剂量依赖方式抑制 irAng II 的释放（p < 0.001），并且它（10^(-6)M）导致 irAng I 释放的相应增加（p < 0.05）。卡托普利（50 mg/kg/天）口服预处理 1 周可使 irAng II 的释放抑制 31%（p < 0.02）。用一种高度亲脂性的血管紧张素转换酶抑制剂 SA 446 进行相同处理，可使 irAng II 的释放抑制 63%（p < 0.001）。另一方面，这两种抑制剂对血浆 irAng II 的抑制程度非常相似。与单独使用 SA 446 相比，SA 446 加肾切除术预处理并未导致 irAng II 释放发生任何进一步变化。这些结果为外周血管组织局部生成并随后分泌 Ang II 提供了直接证据。
