Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment

Abstract

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.