AT1 antagonist modulates activin-like kinase 5 and TGF-β receptor II in the developing kidney

Previous studies by our group have demonstrated that angiotensin-converting enzyme (ACE) inhibition in the developing kidney modulates transforming growth factor-β receptors. Blocking of angiotensin II (ANG II) mainly through angiotensin II type 1 receptor (AT1) has been implicated in mediating this ACE inhibition. The present study was designed to investigate the effects of an AT1 antagonist, losartan, on transforming growth factor-β1 (TGF-β1), TGF-β receptor I [TβRI, activin-like kinase (ALK)-1, ALK-5], TGF-β receptor II (TβRII), and α-smooth muscle actin (α-SMA) expression in the developing kidney. Newborn rat pups were treated with losartan (30 mg/kg per day) or normal saline for 7 days. Kidneys were removed for immunohistochemistry, reverse transcription polymerase chain reaction (PCR), and Western blotting of TGF-β1, ALK-1, ALK-5, TβRII, and α-SMA. Renal ALK-5 and TβRII protein expressions in the losartan-treated group were found to be significantly increased (P<0.05), whereas TGF-β1, ALK-1, and α-SMA protein expressions were not changed by losartan treatment. The losartan-treated group also showed significantly increased mean tubular diameter and interstitial area of the kidney (P<0.05). These results suggest that AT1 inhibition in the developing kidney impairs renal growth and development and modulates the expression of ALK-5 and TβRII.