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University of Virginia, Children's Medical Center, Charlottesville, Virginia 22908
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.
angiotensin receptors; kidney development
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