When a marked stimulation of the reninangiotensin system induced in the rat by bilateral adrenalectomy and salt-depletion is abruptly blocked by a 48-hr substitution treatment which desoxycorticosterone acetate (DOCA) and saltload, one observes: 1) an absolute increase of a form of renin revealed only after prior acidification (pH, 2.5) of kidney extract before usual incubation at the optimum pH of 6.5 and 2) the simultaneous appearance of many granules containing crystalline cores in the epithelioid cells of the juxtaglomerular apparatus. These observations are compatible with the existence of two forms of renal renin and show that after renin-depletion of the kidney, newly synthesized renin is mainly in the acid-activated form. Storage of this renin the epitheloid cells may possibly take the form of secretory granules with crystalline cores. It is speculated that the acid-activated from of renin may be either a renin proenzyme or a protein-bound form.

1. The morphology of the juxtaglomerular apparatus, plasma renin activity, plasma renin substrate and renal renin have been studied in rats after maximal stimulation by bilateral adrenalectomy and salt depletion, and also after blocking this stimulation by deoxycorticosterone and salt load.2. After stimulation the juxtaglomerular apparatus showed a well-developed granular endoplasmic reticulum and a low secretory granule content.Plasma renin activity was markedly elevated and plasma renin substrate was low. After blockade numerous specific granules with crystalline structures were seen and the granular endoplasmic reticulum was less developed. Plasma renin activity was now low and plasma renin substrate elevated.3. After prior acidification of the kidney extract a significant increase of renal renin was observed in both conditions but was greater in the second group at the time when large numbers of young granules containing crystalline material were seen. 4. Kidney slices from the adrenalectomized saltdepleted rats released more renin than control slices. Vincristine did not affect this release, but inhibited release from slices stimulated by isoprenaline.