Nephrogenesis and angiotensin II receptor subtypes gene expression in the fetal lamb

To investigate the role of angiotensin II (ANG II) in nephrogenesis, a developmental study of renal AT(1) and AT(2) receptor mRNA expression was performed in parallel with the quantitative and qualitative analysis of metanephros development in fetal lamb from 60 to 140 days of gestation. Both ANG II receptor subtypes were expressed early during nephrogenesis but displayed specific spatial and temporal distribution during gestation. High-AT(2) mRNA expression took place in the outermost nephrogenic area and in the undifferentiated mesenchymal cells surrounding the ampulla; level of AT(2) expression in this localization followed closely glomeruli proliferation rate and disappeared after nephrogenesis completion (>120 days). AT(2) mRNA was also detected in the differentiated epithelial cells of macula densa of maturing glomeruli. Although most of AT(1) mRNA labeling was found in the mesangial cells of maturing glomeruli, where it persisted after nephrogenesis completion, additional labeling was found in undifferentiated cells, in cells invading the inferior cleft of S-shaped bodies (80 days), and in medullar cells between tubules (120 days). Our results suggest that each receptor subtype has a specific role in renal morphogenesis, i.e., AT(2) in mesenchymal proliferation or apoptosis and AT(1) in vascular smooth muscle cells differentiation.