Angiotensin II controls angiotensinogen secretion at a pretranslational level

It has been proposed that feedback by angiotensin II, the effector peptide of the renin-angiotensin system stimulates hepatic angiotensinogen synthesis, since long-term infusion of this octapeptide in vivo induced an increase in plasma angiotensinogen concentrations. In the present study, the effects of angiotensin II (9 and 90 nmol/l) on angiotensinogen messenger (m)RNA concentrations and on angiotensinogen secretion of freshly isolated rat hepatocytes were compared with those of glucocorticoids (hydrocortisone, 10(-4) mol/l, and dexamethasone, 10(-5) mol/l). Angiotensin II and the glucocorticoids elevated angiotensinogen mRNA concentrations two- to threefold. Angiotensinogen secretion rates were correspondingly increased with a time lag of about 2 h. Differences in the time-course of changes in mRNA following onset or decay of the hormonal effect suggest that angiotensin II and glucocorticoids express their effects by different intracellular mechanisms. This view is supported by the observation that angiotensin II but not dexamethasone has a stabilizing effect on angiotensinogen mRNA, when further synthesis was blocked by actinomycin D.