Effects of Angiotensin Converting Enzyme Inhibition into Apoptosis and Related Genes in the Neonatal Rat Kidney

ABSTRACT

PURPOSE: The renin-angiotensin system plays an important role in renal growth and development. Exposuring the neonate to angiotensin converting enzyme(ACE) inhibitor increases mortality and results in growth retardation and abnormal renal development. ACE inhibition in the developing kidney reduces the renal expression of TGF-beta1 and EGF, which may account for renal growth impairment. This study was designed to investigate the relationship between this growth impairment, and apoptosis, cell proliferation, bcl-2 and clusterin expression. METHODS: Newborn rat pups were treated with enalapril(30mg/kg/d) or vehicle for 7 days and kidneys were removed for RT-PCR and Western blotting of bcl-2 and clusterin. Distribution of apoptosis was determined by modified TUNEL technique and PCNA for cell proliferation was stained by immunohistochemistry. RESULTS: Enalapril treatment resulted in 24% mortality by day 7 and reduced body weight(P< 0.05 versus vehicle group). Enalapril increased renal apoptosis and decreased PCNA positive proliferating cells especially in cortical tubular epithelial cells(P<0.05). Renal bcl-2 and clusterin mRNA expression was increased(P<0.05), but bcl-2 and clusterin protein expression was decreased by enalapril treatment. CONCLUSION: These results indicate that ACE inhibition in the developing kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. Bcl-2 and clusterin mRNA expression may increase as a secondary response to increased apoptosis and decreased their protein expression.