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

Am J Physiol Regul Integr Comp Physiol. 2000 Sep;279(3):R1050-60. doi: 10.1152/ajpregu.2000.279.3.R1050.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / drug therapy
  • Abnormalities, Drug-Induced / physiopathology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Animals, Newborn
  • Enalapril / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / pharmacology*
  • Kidney Concentrating Ability / physiology
  • Kidney Cortex / abnormalities*
  • Kidney Cortex / embryology
  • Kidney Cortex / enzymology
  • Kidney Function Tests
  • Kidney Medulla / abnormalities
  • Kidney Medulla / embryology
  • Kidney Medulla / enzymology
  • Male
  • Osmolar Concentration
  • Peptidyl-Dipeptidase A / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptor, IGF Type 1 / genetics
  • Receptors, Somatotropin / genetics
  • Renal Circulation / physiology
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*


  • Angiotensin-Converting Enzyme Inhibitors
  • RNA, Messenger
  • Receptors, Somatotropin
  • Insulin-Like Growth Factor I
  • Enalapril
  • Receptor, IGF Type 1
  • Peptidyl-Dipeptidase A