IGF-I treatment attenuates renal abnormalities induced by neonatal ACE inhibition

An intact renin-angiotensin system (RAS) during nephrogenesis is essential for normal renal development. We have shown previously that neonatal inhibi tion of the RAS, either with ANG II type 1-receptor blockade or angiotensin -converting enzyme (ACE) inhibition, induces irreversible renal abnormaliti es. The aim of the present study was to investigate whether an interrupted RAS can be compensated for by exogenous administration of another important renal growth-promoting factor, the insulin-like growth factor-I (IGF-I). R ats were treated daily with either the ACE inhibitor enalapril (10 mg/kg), recombinant human IGF-I (3 mg/kg), or the combination enalapril 1 IGF-I fro m perinatal day 3 to 13. Urinary concentrating ability, renal function, and renal morphology were assessed at adult age. The gene expression and local ization of IGF-I, its receptor, and the growth hormone receptor (GHR) were investigated during ongoing ACE inhibition. The present study demonstrates normalized renal function and histology in enalapril 1 IGFI-treated animals . Ongoing ACE inhibition suppressed the medullary IGF-I mRNA expression and altered the local distribution of both IGF-I and GHR. Thus the present stu dy provides evidence for an interaction between the RAS and GH/IGF-I axis i n renal development.