Renin processing and secretion in adrenal and retina of transgenic (mREN-2)27 rats

Two extrarenal tissue sources of renin were studied using quantitative assays and immunocytochemical methods during 12 hours following binephrectomy (BNx) in anesthetized hypertensive homozygous Ren-2 transgenic (TG) rats maintained off hypotensive drugs for three weeks. Compared to normal rats, circulating active renin was depressed 50% in conscious TG rats and prorenin was 5- to 10-fold higher. Post-BNx, arterial active and prorenin increased progressively to 10-fold, at which time adrenal venous outputs were 0.1 and 20 mGU/min, respectively. The ratio of active to prorenin (3.1 +/- 0.6%) remained unchanged with increasing plasma levels. Thus, either intrinsic enzyme activity of the transgenic prorenin contributed a constant proportion to the measured active renin, or processing to mature renin was coupled to prorenin synthesis and secretion in extrarenal tissues. In the TG rat eye, renin protein labeling was localized throughout retinal Müller cells with prosequence more obvious posteriorly, consistent with directional processing. Immunogold studies are in progress. In adrenal following BNx, labeling for renin and prosequence increased uniformaly in all zones of the cortex and in scattered medullary chromaffin cells. In cortex, both renin and prosequence were strongly located in intramitochondrial dense bodies. In chromaffin cells, renin labeling was present in both cytoplasmic vesicles and electron-dense granules, while prosequence was predominantly in cytoplasmic vesicles, consistent with processing of prorenin prior to storage in chromaffin granules.