Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney

Objectives. To investigate whether partial ureteral obstruction (PUO) in the fetus induces dysregulation of the renin-angiotensin system (RAS) and of transforming growth factor-beta 1 (TGF-β1) and tissue inhibitors of metalloproteinase (TIMP1) expression. Previous studies have indicated that renal and urinary tract development depend on an intact renal RAS. Fetal urinary obstruction is distinct from postnatal obstruction. It has been suggested in postnatal animal studies that dysregulation of the RAS, and subsequent increased expression of TGF-β1 and TIMP1, leads to changes in extracellular matrix composition. Methods. Bilateral PUO was created in 4 fetal sheep. Seven animals (four obstructed and three controls) were killed at birth and their kidneys removed. Semiquantitative reverse transcriptase-polymerase chain reaction was used to quantify the levels of renin, angiotensinogen, angiotensin receptor type 1 (AT1 receptor), angiotensin receptor type 2 (AT2 receptor), TGF-β1, and TIMP1. These messages were normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA. Results. All obstructed animals had moderate to severe hydronephrosis with enlarged kidneys (mean weight 22.0 g versus 9.4 g for the control animals; P