Blumberg A L, Sealey J E, Atlas S A, Laragh J H, Dharmgrongartama B, Kaplan A P
J Lab Clin Med. 1981 Jun;97(6):771-8.
Acid activation of plasma prorenin occurs during dialysis to pH 3.3. and also during subsequent dialysis to pH 7.4. The latter, alkaline phase, involves Hageman factor-dependent formation of kallikrein, which in turn activates prorenin. The present study evaluates whether prorenin activation always occurs whenever kallikrein is activated in plasma. TAME esterase activity was used as a measure of plasma kallikrein activity an increase was observed during the alkaline phase of acid activation of prorenin. TAME esterase activity was absent when Hageman factor- or prekallikrein-deficient plasmas were similarly assayed and prorenin was not activated. Kaolin treatment of normal plasma rapidly increased TAME esterase activity at both 25 degrees and -4 degrees C, but no prorenin activation occurred. Similar changes in TAME esterase activity were observed in acid-treated plasma, in which setting prorenin was activated. No change in TAME esterase or renin activity occurred after addition of kaolin to acid-treated plasma deficient in Hageman factor; however, both enzymatic activities increased slightly in acidified prekallikrein-deficient plasma. Mixtures of these deficient plasmas exhibited normal kaolin activation of both TAME esterase and prorenin after acidification. Thus both Hageman factor and prekallikrein are needed for optimal contact activation of prorenin. These results demonstrate that prorenin activation does not always occur when active kallikrein is present in plasma. Prior acidification appears to be a prerequisite. Acidified prorenin may be more susceptible to cleavage; alternatively, competing substrates and/or inhibitors of kallikrein may be destroyed at acid pH, thereby permitting kallikrein to activate prorenin. Under normal conditions, activation of the plasma kallikrein-kinin system appears unlikely to result in activation of prorenin in vivo.
血浆中血管紧张素原的酸激活在透析至pH 3.3时发生，也在随后透析至pH 7.4时发生。后者的碱性阶段涉及依赖于哈格曼因子的激肽释放酶形成，激肽释放酶进而激活血管紧张素原。本研究评估血浆中激肽释放酶被激活时血管紧张素原是否总会被激活。使用对甲苯磺酰-L-精氨酸甲酯（TAME）酯酶活性作为血浆激肽释放酶活性的指标，在血管紧张素原酸激活的碱性阶段观察到其活性增加。当对缺乏哈格曼因子或前激肽释放酶的血浆进行类似检测时，未检测到TAME酯酶活性，且血管紧张素原未被激活。在25℃和 -4℃下，用高岭土处理正常血浆可迅速增加TAME酯酶活性，但未发生血管紧张素原激活。在酸处理的血浆中观察到TAME酯酶活性有类似变化，在此情况下血管紧张素原被激活。向缺乏哈格曼因子的酸处理血浆中添加高岭土后，TAME酯酶或肾素活性未发生变化；然而，在酸化的缺乏前激肽释放酶的血浆中，两种酶活性均略有增加。这些缺乏血浆的混合物在酸化后对高岭土激活TAME酯酶和血管紧张素原均表现出正常反应。因此，哈格曼因子和前激肽释放酶都是血管紧张素原最佳接触激活所必需的。这些结果表明，当血浆中存在活性激肽释放酶时，血管紧张素原并不总会被激活。预先酸化似乎是一个先决条件。酸化的血管紧张素原可能更易被裂解；或者，激肽释放酶的竞争性底物和/或抑制剂可能在酸性pH下被破坏，从而使激肽释放酶能够激活血管紧张素原。在正常情况下，血浆激肽释放酶-激肽系统的激活在体内似乎不太可能导致血管紧张素原的激活。
