ACE inhibition modulates transforming growth factor-β receptors in the young rat

The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-β1 (TGF-β1), TGF-β receptor I [TβRI, activin-like kinase (ALK)-1 and ALK-5], and TGF-β receptor II (TβRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-β1, ALK-1, ALK-5, and TβRII, and for RT-PCR of ALK-5 and TβRII TGF-β1, ALK-1, ALK-5, and TβRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight (P<0.05 versus vehicle). Enalapril decreased renal TGF-β1, ALK-1, and ALK-5 protein expression (P<0.05). Also, enalapril decreased ALK-5 mRNA expression (P<0.05). TβRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-β1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TβRII may not be modulated by ACE inhibition in the developing kidney.