Angiotensinogen production and consumption in the adrenalectomized rat.
The aim of this study was to investigate the mechanisms by which angiotensinogen decreases after adrenalectomy. Plasma angiotensinogen was measured by two different methods: an indirect assay, which measures angiotensin I liberated from the plasma by an excess of renin, and a direct RIA, which measures both angiotensinogen and des-angiotensin I-angiotensinogen. In the normal rat angiotensinogen concentrations were found to be slightly, but not significantly, higher using the direct assay. After adrenalectomy a large discrepancy was observed between the indirect assay, which showed a considerable drop in plasma angiotensinogen levels, and the direct assay, which revealed a small but significant decrease. This discrepancy arose from the presence of a molecule that cross-reacts with angiotensinogen antibodies, and has a more acidic pI in isoelectric focusing than angiotensinogen: des-angiotensin I-angiotensinogen. This molecule accumulates in adrenalectomized rat plasma. The decrease in plasma angiotensinogen levels, measured by the indirect assay, could not be explained by a decrease in angiotensinogen production, as this was unchanged in the in vitro liver slice system, but was caused by an increase in angiotensinogen consumption, due to a rise in the plasma concentration of renin. Renin concentration shows a negative correlation with angiotensinogen (as measured by the indirect assay), and a positive correlation with des-angiotensin I-angiotensinogen level. Moreover, mineralocorticoids were shown to correct both renin and angiotensinogen concentrations, whereas a replacement dose of glucocorticoids (dexamethasone) had no effect on the level of renin or angiotensinogen, as measured by the indirect assay. We conclude that after adrenalectomy, plasma angiotensinogen decreases, due to an increase in renin production. A parallel accumulation of des-angiotensin I-angiotensinogen is observed.
D000315:Adrenalectomy; D000803:Angiotensin I / Q000097:blood / Q000031:analogs & derivatives; D000808:Angiotensinogen / Q000096:biosynthesis / Q000097:blood*; D000809:Angiotensins / Q000097:blood*; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D007525:Isoelectric Focusing; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D000809:Angiotensins; D010446:Peptide Fragments; C018899:des-angiotensin I renin substrate; D000808:Angiotensinogen; D003900:Desoxycorticosterone; D003907:Dexamethasone; D000803:Angiotensin I; D012083:Renin