ONTOGENY OF ANGIOTENSINOGEN MESSENGER-RNA AND ANGIOTENSIN-II RECEPTORS IN RAT-BRAIN AND LIVER

The renin-angiotensin-system (RAS) is active in fetal and neonatal life. This study was undertaken to examine the ontogenic regulation of angiotensinogen (AT) gene expression and angiotensin II (A II) receptors in liver and brain. AT gene expression was studied in fetal, neonatal, adult and aged rats, using slot blot hybridization to quantify AT mRNA levels. During fetal life (gestational days 15-20), AT mRNA was more abundant in brain than in liver. Soon after birth, brain AT mRNA levels increased to a concentration 3 fold above fetal levels. In contrast, liver AT mRNA abundance increased 30-fold within 12 h of birth. Aging (3-20 months) resulted in a gradual decrease in AT mRNA in both the brain and liver. Liver A II receptors in the neonate were 2-fold higher than in the fetus, but returned to fetal levels by 8 weeks of age. In the brain, A II receptor abundance increased to a level 75% above fetal levels in 7 day old animals, but returned to fetal levels by 14 days of age. These studies suggest than in the fetus, the liver is not the primary source of AT but that unknown factors at parturition result in a dramatic increase in liver AT mRNA. In contrast, the more modest increases in brain AT mRNA parallel the gradual maturation of the CNS. In both tissues, further aging resulted in a gradual decrease in AT mRNA, reflecting either increased sensitivity to feedback downregulation by A II or age related increases in other extrahepatic sites of AT synthesis. Age related changes were also found in the A II receptor in both the liver and brain.