Studies on Angiotensinogen Formation in a Liver Perfusion System
- Nasjletti, Alberto M.D.
- Masson, M. C. Ph.D.
Isolated rat livers perfused with an angiotensinogen-free medium were used to demonstrate the hepatic origin of the substrate of renin and to measure its rate of production under various experimental conditions. Rates of angiotensinogen formation and incorporation of radiolabeled amino acids into proteins were measured during periods of perfusion up to eight hours.
Normal livers produced substrate at a rate of 12 ng/hr/g of tissue. After nephrectomy, rates of substrate formation increased gradually during the first 12 hours to a peak about nine times above normal, then decreased after 48 hours to levels still higher than normal. Ureteral ligation, partial hepatectomy, and treatment with mercuric bichloride or with stilbestrol markedly enhanced the production of substrate without affecting the incorporation of labeled amino acids into proteins, with the exception of partial hepatectomy, which caused a two- to threefold rise in protein synthesis. Stilbestrol had a direct stimulating effect on substrate synthesis, as was shown when this estrogen was added to the perfusion fluid. Adrenalectomy increased substrate formation slightly.
Inhibition of substrate synthesis by puromycin and the presence of only minute amounts of substrate in liver homogenates suggest that at least 90% of the substrate released by the liver is newly synthesized. The other 10% may originate either from plasma trapped in the hepatic vascular bed or from small hepatic storage. Determination of rates of substrate formation together with plasma renin concentration permits a more accurate estimation of the mechanisms regulating angiotensinogen levels in plasma, since it is likely that these levels are the result of an equilibrium between synthesis and destruction.