The regulatory mechanism for renin substrate synthesis by the liver

Abstract

The regulatory mechanism for renin substrate synthesis by the liver was investigated under various experimental conditions in rats, using an isolated liver perfusion and isolated hepatocytesm Insulin and thyroxine stimulated the synthesis of renin substrate, while glucagon, angiotensin II and prostaglandin (PG) F₂α had no effect on substrate formation. The treatment with 17 β-estradiol increased renin substrate synthesis with producing an additional form of substrate with a different isoelectric point from that of normal form of substrate. The remarkable increase in renin substrate synthesis after bilateral nephrectomy was significantly suppressed by the treatment with PGE1 or PGE₂. These findings suggest that a high level of plasma renin activity (PRA) observed in the patients with hyperthyroidism or low PRA in the patients with diabetes mellitus may be due to the stimulated or suppressed synthesis of renin substrate by the liver as well as the changes in plasma renin concentration. This study also suggests that PGE₂ is one of the inhibitory factors originating from the kidney on renin substrate synthesis by the liver.