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

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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.