Novel expression and regulation of the renin-angiotensin system in metanephric organ culture

Abstract

To evaluate the presence and regulation of the renin-angiotensin system (RAS) in metanephric organ culture, embryonic day 14 (E14) rat metanephroi were cultured for 6 days. mRNAs for renin and both ANG II receptors (AT1 and AT2) are expressed at E14, and all three genes continue to be expressed in culture. Renin mRNA is localized to developing tubules and ureteral branches in the cultured explants. At E14, renin immunostaining is found in isolated cells scattered within the mesenchyme. As differentiation progresses, renin localizes to the ureteric epithelium, developing tubules and glomeruli. E14 metanephroi contain ANG II, and peptide production persists in culture. Renin activity is present at E14 (6.13 ± 0.61 pg ANG I · kidney−1 · h−1) and in cultured explants (28.84 ± 1.13 pg ANG I · kidney−1 · h−1). Renin activity in explants is increased by ANG II treatment (70.1 ± 6.36 vs. 40.97 ± 1.94 pg ANG I · kidney−1 · h−1 in control). This increase is prevented by AT1 blockade, whereas AT2 antagonism has no effect. These studies document an operational local RAS and a previously undescribed positive-feedback mechanism for renin generation in avascular, cultured developing metanephroi. This novel expression pattern and regulatory mechanism highlight the unique ability of developing renal cells to express an active RAS.