Abstract
We investigated the biochemical properties of plasma inactive renin from patients with diabetic hyporeninemic hypoaldosteronism (DHH) and its mechanism of activation. The plasma renin activity (PRA) of the patients with DHH was extremely low, but their inactive renin was increased compared to that of normal subjects. The molecular weight (MW) of the plasma inactive renin was 55, 000 as determined with Sephadex G-100, and 50, 000 as determined with Ultrogel AcA 44. The isoelectric points (pI) of the plasma inactive renin were 5.3, 5.5, 5.75 and 6.1, indicating that the inactive renin had multiple components. These MW and pI values for plasma inactive renin from the diabetic patients were the same as those of normal human plasma. We then studied the activation mechanism of the plasma inactive renin of the patients with DHH. With the trypsin activation method, the MW changed from 50, 000 to 42, 000 as determined using Ultrogel AcA 44 and the p1 values shifted towards acidic pHs of 4.6, 4.75, 4.9 and 5.1. With the acid activation method, the MW was reduced to 42, 000 and the pI values changed to 4.58, 5.0, 5.2, 5, 35 and 5.55, which were analogous to those of renal active renin. The increased inactive renin in DHH patients had the same biochemical properties as those observed in healthy individuals and the pI values were similar to those of renal prorenin. These results suggest that the increased plasma inactive renin in DHH patients was caused by impaired conversion from prorenin to active renin in the kidney. As regards the activation method, inactive renin activated with trypsin had a different molecular structure from circulating active renin, whereas by acid activation, the inactive renin was converted to active renin with the same molecular structure as that of renal active renin.
