Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment.
Lack of neonatal angiotensin II type-1 receptor stimulation produces irreversible abnormalities of renal function and morphology, which can be prevented by simultaneous administration of insulin-like growth factor-I (IGF-I). Given the fact that growth hormone (GH) is the strongest secretagogue for IGF-I, we wanted to explore whether GH could reproduce the effect of IGF-I. Rats were treated from 3 to 13 days of age with the angiotensin-converting enzyme inhibitor enalapril (10 mg/kg/day) and GH (4 mg/kg/day), alone or in combination. Renal gene expression of IGF-I and IGF-binding proteins (IGFBP) was determined during and after treatment. Renal function and morphology were investigated at adult age. In contrast to the beneficial effect of IGF-I, GH treatment in combination with enalapril further deteriorated both renal function and morphology as compared with enalapril treatment alone, demonstrating: reduced glomerular filtration rate, increased tubular dilation and further expansion of the outer medulla. Enalapril decreased medullary expression of IGF-I and increased renal expression of IGFBP-1, changes that were not affected by concomitant GH treatment. These findings indicate that GH and IGF-I have different roles in the renin-angiotensin system-mediated kidney development.
Nilsson
Annika B M
AB
Department of Physiology, University of Gothenburg, 405 30 Gothenburg, Sweden.
Friberg
Peter
P
Bönquist
Linda
L
Lasaitiene
Daina
D
Marcussen
Niels
N
Chen
Yun
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D019382:Human Growth Hormone / Q000494:pharmacology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000254:growth & development* / Q000473:pathology* / Q000502:physiology; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D004656:Enalapril