ONTOGENY OF RENIN AND AT1 RECEPTOR IN THE RAT

The enzyme renin and the angiotensin II (Ang II), subtype I receptor ( ATI) are developmentally regulated in a tissue-specific manner. In ear ly life, renin is expressed widely along the renal vasculature. As mat uration progresses, there is a decrease in renin mRNA levels and a shi ft in the localization of renin close to the glomerulus. In addition, in the newborn rat, the number of renin-secreting cells is higher than in the adult rat. Exposure of neonatal and adult cells to Ang II resu lts in a decrease of similar magnitude in the number of renin-secretin g cells. These findings suggest that the high levels of renin observed in immature animals are due to increased renin synthesis and release rather than to a blunted response to Ang II. Expression of the ATI gen e is also developmentally regulated in a tissue-specific manner. With maturation, ATI mRNA levels decrease in the kidney while they increase in the liver. The localization of ATI transcripts in precursor cells of the nephrogenic cortex suggests a role for this receptor in nephron growth and development. Inhibition of ATI with DUP753 results in dela yed kidney and somatic growth and in increased renin mRNA levels and r ecruitment of renin-containing cells. These observations suggest that Ang II exerts a tonic negative feedback on renin gene expression via t he ATI receptor subtype. Further studies are necessary to delineate th e molecular and cellular signals mediating these developmental changes .