Inhibition of human renin by rat plasma. Rat angiotensinogen is a competitive inhibitor of the human renin-substrate interaction.
Inhibition of human renin by rat plasma. Rat angiotensinogen is a competitive inhibitor of the human renin-substrate interaction.
复制标题
大鼠血浆对人肾素的抑制。
DOI：
10.1093/ajh/5.8.495
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发表时间：
1992
影响因子：
3.2
通讯作者：
Laragh,JH
中科院分区：
文献类型：
--
作者：
Gahnem,F;Sealey,JE;Atlas,SA;Laragh,JH
人的肾素可以裂解大鼠血管紧张素原，但输注人的肾素到大鼠只会导致血压适度升高。因此，我们研究了大鼠血浆中是否存在抑制人肾素活性的因子。向人血浆中加入20%正常大鼠血浆对血管紧张素形成速率有轻微但不显著的抑制作用，而肾切除大鼠血浆（其血管紧张素原浓度高7倍）引起剂量依赖性抑制（20 - 70%）。大鼠血浆抑制剂与血管紧张素原共纯化。分析人肾素-人底物反应的动力学和人肾素-人底物反应的动力学。大鼠底物反应表明，在两种底物存在下，血管紧张素I的产生速率可以完全通过假设大鼠和人血管紧张素原是彼此的竞争性抑制剂来解释。这些结果表明，人肾素可以切割大鼠底物，但反应速率相对于人的切割非常慢。血管紧张素原他们还表明，大鼠血管紧张素原是一种有效的竞争性抑制剂的人肾素底物反应。这些结果可能是相关的发展，肾素抑制剂和转染研究涉及异源肾素或底物基因。美国高血压杂志1992;5：495-501
Human renin can cleave rat angiotensinogen, yet infusion of human renin into rats causes only a modest increase in blood pressure. We therefore investigated whether there is a factor in rat plasma which inhibits human renin activity. The addition of 20% normal rat plasma to human plasma had a slight, but not significant, inhibitory effect on the rate of angiotensin formation, while nephrectomized rat plasma, which had a seven-fold higher concentration of angiotensinogen, caused a dose dependent inhibition (20 to 70%). The rat plasma inhibitor copurified with angiotensinogen. Analysis of the kinetics of the human renin-human substrate reaction and of the human renin-rat substrate reaction revealed that the rate of angiotensin I production in the presence of both substrates could be entirely accounted for by assuming that rat and human angiotensinogens are competitive inhibitors of each otherThese results show that human renin can cleave rat substrate but the reaction rate is extremely slow relative to the cleavage of human angiotensinogen. They also indicate that rat angiotensinogen is an effective competitive inhibitor of the human reninsubstrate reaction. These results may be relevant to the development of renin inhibitors and to transfection studies involving heterologous renin or substrate genes. Am J Hypertens 1992;5:495–501