Production of Active and Inactive Renin by Adrenal Explant Cultures and the Existence of a Prorenin Activating Enzyme in the Adrenal Gland

: We previously demonstrated high levels of inactive renin (IR) in nephrectomized rat plasma which provided evidence for extra-renal sources of IR. However, the sources of IR were unknown. This study examined whether the adrenal gland is capable of producing active renin (AR) and IR, using explants of adrenal capsules (glomerulosa portions) from control and nephrectomized (Nepex) rats. Explants from both control and Nepex rats produced large quantities of IR and small quantities of AR. The productions of both IR and AR in Nepex rats were significantly greater than in control rats. High potassium culture medium markedly increased IR and slightly, but significantly, enhanced AR in both control and Nepex rats. On the other hand, sodium had little effect on either IR or AR. A renin-angiotensin system has been reported in the adrenal gland. Recently, a prorenin activating enzyme was demonstrated in the kidney and the aortic wall. The next study was performed to demonstrate the existence of a prorenin activating enzyme in the adrenal gland, using inactive renin from culture medium from Nepex rat explants as the substrate. A 26 KD component in adrenal zona glomerulosa tissues isolated by Sephacryl S-200 column chromatography, converted IR to AR in IR rich medium. The pH optimum for prorenin activation by the enzyme was 6.5. Inhibitor studies indicate that this enzyme is a serine protease. These data suggest that (1) the adrenal gland is an extra-renal source of inactive renin and (2) a prorenin activating enzyme exists in the adrenal gland.