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Am J Physiol Regul Integr Comp Physiol 279: R1050-R1060, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 3, R1050-R1060, September 2000

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

Annika B. M. Nilsson1, Nicoleta Nitescu1, Yun Chen1, Gregor S. Guron1, Niels Marcussen2, Göran L. Matejka3, and Peter Friberg1,4

1 Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Medicinaregatan 11, S-413 90 Göteborg; 3 Department of Internal Medicine and 4 Clinical Physiology, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden; and 2 University Institute of Pathology, Aarhus Kommunehospital, DK-8000 Aarhus, Denmark

An intact renin-angiotensin system (RAS) during nephrogenesis is essential for normal renal development. We have shown previously that neonatal inhibition of the RAS, either with ANG II type 1-receptor blockade or angiotensin-converting enzyme (ACE) inhibition, induces irreversible renal abnormalities. 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). Rats were treated daily with either the ACE inhibitor enalapril (10 mg/kg), recombinant human IGF-I (3 mg/kg), or the combination enalapril + IGF-I from perinatal day 3 to 13. Urinary concentrating ability, renal function, and renal morphology were assessed at adult age. The gene expression and localization 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 + IGF-I-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 study provides evidence for an interaction between the RAS and GH/IGF-I axis in renal development.

renin-angiotensin system; renal development; angiotensin-converting enzyme; insulin-like growth factor


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