The Feedback Regulation of Angiotensinogen Production by Components of the Renin-angiotensin System

The in vivo generation of angiotensin appears to be dependent on both plasma renin and angiotensinogen concentrations. Much less is known about the control of hepatic angiotensinogen synthesis and release, as compared to that of renin. In this study, we examined the feedback regulation of angiotensinogen synthesis and release by various components of the renin-angiotensin system, using an in vitro rat liver slice system. Livers were removed for study from rats which were subjected to various systemic infusions or physiological perturbations. Infusion of angiotensin II has been reported to increase angiotensinogen release rate. However, infusion of angiotensin I (with simultaneous suppression of plasma renin by antirenin antibody infusion and angiotensin II production by captopril administration) had no effect on the angiotensinogen release rate. Direct infusion of renin in rats treated with captopril resulted in further suppression of the angiotensinogen release rate, compared with those given captopril alone. We postulate that renin (or des-angiotensin I-angiotensinogen) inhibits the angiotensinogen release rate, whereas angiotensin II stimulates it. Angiotensin I has no effect on angiotensinogen release rate. This hypothesis was evaluated further in rats with various physiological states. Indeed, when conditions were such that the renin-angiotensin system was completely suppressed, such as binephrectomy and antirenin antibody infusion, angiotensinogen release rate was markedly stimulated. When angiotensin II production was prevented by captopril treatment, angiotensinogen release rate declined. This appeared to be the case for all states of sodium balance. Thus, angiotensinogen release rate is subject to a complex feedback control by other components of the renin-angiotensin system.