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 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)

Nyckelord

Abnormalities

Drug-Induced

drug therapy

physiopathology

Angiotensin-Converting Enzyme Inhibitors

pharmacology

Animals

Animals

Newborn

Enalapril

pharmacology

Gene Expression Regulation

Developmental

drug effects

physiology

Insulin-Like Growth Factor I

genetics

pharmacology

Kidney Concentrating Ability

physiology

Kidney Cortex

abnormalities

embryology

enzymology

Kidney Function Tests

Kidney Medulla

abnormalities

embryology

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

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)