Okunishi H, Miyazaki M, Toda N
J Hypertens. 1984 Jun;2(3):277-84.
An inhibitor of angiotensin I (ANG I) converting enzyme, SA446, reduced the response to ANG I of blood vessels isolated from dogs and monkeys, but did not abolish the response even at high concentrations. The residual action of ANG I in the presence of high concentrations of SA446 could be abolished by (Sar1, Ala8)-ANG II. Vascular strips and crude extracts of vessels and lungs possessed the enzymic activity generating ANG II from ANG I, or hippuric acid from hippuryl-histidyl-leucine (HHL). The HHL-hydrolysing activity of the crude extracts was completely inhibited by SA446 (10(-7) mol/l) and/or Na2-EDTA (10(-3) mol/l). However, the octapeptide generation was not abolished despite the combined treatment with SA446 (5 X 10(-4) mol/l) and Na2-EDTA (5 x 10(-3) mol/l). The residual activity forming ANG II was inhibited by chymostatin and soybean trypsin inhibitor, which however did not affect the HHL-hydrolysis. Combined treatment with SA446 (10(-5) mol/l) and chymostatin (2.5 X 10(-5) mol/l) abolished the vascular action of ANG I but did not alter the action of ANG II. These results strongly suggest that besides the ANG I converting enzyme, another enzyme which generates ANG II is present in vascular tissues and lungs, and may play an important role in the local generation of ANG II, which possibly regulates the regional vascular tone.
血管紧张素I（ANG I）转化酶抑制剂SA446可降低从犬和猴分离出的血管对ANG I的反应，但即使在高浓度下也不能完全消除该反应。在高浓度SA446存在时ANG I的残余作用可被（Sar1，Ala8）-ANG II消除。血管条以及血管和肺的粗提物具有将ANG I转化为ANG II或从马尿酰-组氨酰-亮氨酸（HHL）生成马尿酸的酶活性。粗提物的HHL水解活性被SA446（10^(-7)mol/L）和/或Na2-EDTA（10^(-3)mol/L）完全抑制。然而，尽管联合使用SA446（5×10^(-4)mol/L）和Na2-EDTA（5×10^(-3)mol/L），八肽生成并未被消除。形成ANG II的残余活性被抑肽酶和大豆胰蛋白酶抑制剂抑制，然而这两种抑制剂并不影响HHL水解。SA446（10^(-5)mol/L）和抑肽酶（2.5×10^(-5)mol/L）联合处理可消除ANG I的血管作用，但不改变ANG II的作用。这些结果强烈表明，除了ANG I转化酶外，血管组织和肺中还存在另一种生成ANG II的酶，它可能在ANG II的局部生成中起重要作用，而ANG II可能调节局部血管张力。
