Action of Angiotensins I, II, and III on Aldosterone Production by Isolated Rat Adrenal Zona Glomerulosa Cells: Importance of Metabolism and Conversion of Peptidesin Vitro*

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Abstract
The steroidogenic activity of angiotensin I (AI), angiotensin II (All), and [des-Asp1]angiotension II (AIII) were assessed using dispersed rat adrenal zona glomerulosa cell incubations. Aldosterone and corticosterone outputs were measured by RIA. All at concentrations as low as 10−12m significantly increased the output of both steroids and had a maximal effect at 10−8m. AIII had a potency relative to All of approximately 0.3% and a threshold dose of near 10−8m. Measurement of the survival of the peptides by both pressor bioassay and RIA revealed that AIII was degraded faster than All during incubation. The source of this peptidase activity was predominantly from the albumin in the medium. However, in medium containing albumin free from peptidase, a similar difference in the potencies of All and AIII was observed, and degradation of AIII but not All was found in the presence of glomerulosa cells. AI had a steroidogenic potency intermediate between All and AIII, with a potency relative to All of approximately 4%, and threshold and maximal concentrations of 10−10 and 10−6m, respectively. However, conversion of AI to All during incubation was demonstrated using RIAs. Furthermore, blockade of converting enzyme during the incubations with SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) led to a marked fall in activity of AI, so that its potency relative to All was reduced to approximately 0.2%. These results demonstrate that All can stimulate steroid output of rat glomerulosa cells at very low concentrations and strongly support a role for All in the physiological control of aldosterone secretion in the rat. The low activity of AIII in this system is probably related to its rapid degradation. AI appears to owe most of its activity to conversion in vitro to All and probably has only low intrinsic activity. These findings highlight the need to assess peptide metabolism during in vitro incubations. (Endocrinology106: 1760, 1980)