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Role of renin substrate in the pressor mechanism and physiological significance of des-angiotensin I renin substrate

肾素底物在升压机制中的作用及去血管紧张素I肾素底物的生理意义

基本信息

批准号：
60480231
负责人：
HIWADA Kunio
金额：
$ 3.01万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

The renin-angiotensin system plays an important role in the regulation of blood pressure, and water and electrolyte balance. In this study we measured plasma renin substrate concentration in normal subjects, pregnant women and hemodyalysis patients using the direct and indirect methods. The values measured by the direct assay always showed higher than that by the indirect assay. This was due to the cross-reaction of the antibody to renin substrate with des-angiotensin I renin substrate. A high PRA in pregnant women is due to higher levels of plasma renin substrate and a high PRA in hemodyalysis patients is due to higher levels of plasma renin concentration.A high molecular weight renin substrate (Mr. 332K daltons) was prepared from plasma of pregnant women. The molecular weight was reduced to 81K by treatment with dithiothreitol (DTE), but not by treatment with SDS. DTT-treated high molecular weight renin substrate was very similar to low molecular weight renin substrate. The antibody against low molecular weight renin substrate completely crossreacted with high molecular weight renin substrate. Our results suggest that high molecular weight renin substrate is probably a complex of low molecular weight renin substrate and other protein(s) which might be bound by disulfide bond.We prepared an affinity column using a specific human renin inhibitor (ES-305) as a ligand and purified stable human renin from kidneys. We also purified human renin substrate from plasma pool by the modified our previous method. Des-angiotensin I renin substrate was prepared by incubating the purified human renin substrate with the purified renin. The physiological significance of des-angiotensin I renin substrate is under investigation.

肾素-血管紧张素系统在调节血压、水电解质平衡中起重要作用。本文采用直接法和间接法测定了正常人、孕妇和血液透析患者血浆肾素底物浓度。直接法测得的结果总是高于间接法。这是由于抗肾素底物抗体与去血管紧张素I肾素底物发生交叉反应。妊娠妇女PRA升高是由于血浆中肾素底物水平升高，而血液透析患者PRA升高是由于血浆中肾素浓度升高。用二硫苏糖醇（DTE）处理可使分子量降至81 K，而用SDS处理则不然。DTT处理的高分子量肾素底物与低分子量肾素底物非常相似。抗低分子量肾素底物抗体与高分子量肾素底物完全交叉反应。结果表明，高分子量的肾素底物可能是低分子量的肾素底物与其它蛋白质的复合物，它们可能通过二硫键结合，我们以特异性的人肾素抑制剂（ES-305）为配基，制备了亲和层析柱，从肾脏中纯化了稳定的人肾素。我们还用改进的方法从血浆池中纯化了人肾素底物。通过将纯化的人肾素底物与纯化的肾素孵育来制备去血管紧张素I肾素底物。去血管紧张素I肾素底物的生理意义正在研究中。