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.

Further insights into the role of angiotensin II in kidney development

“…In addition to the direct growth-promoting activity, ANG II may stimulate other growth factors of importance for kidney development. In this regard, we found a decrease in expression of insulin-growth factor-I (IGF-I) and an increase in expression of IGF-binding protein-1, known to suppress IGF-stimulated effects, in the neonatal RAS-inhibited kidneys (Nilsson et al, 2000(Nilsson et al, , 2003. Moreover, the supplementation of IGF-I prevented in part development of renal abnormalities, suggesting a cross-talk between the RAS and IGF-I signalling in postnatal nephrogenesis in the rat (Nilsson et al, 2000).…”

“…2). In this regard, we found a decrease in expression of insulin-growth factor-I (IGF-I) and an increase in expression of IGF-binding protein-1, known to suppress IGF-stimulated effects, in the neonatal RAS-inhibited kidneys (Nilsson et al, 2000(Nilsson et al, , 2003. In addition to the direct growth-promoting activity, ANG II may stimulate other growth factors of importance for kidney development.…”

The renin–angiotensin system in kidney development

“…In support of this notion, we have demonstrated that neonatal enalapril treatment in rats produces a reduction in insulin‐like growth factor‐I (IGF‐I) mRNA levels specifically in the renal medulla (Nilsson et al. 2000, 2003), as well as an increment in IGF‐binding protein 1 (IGFBP1) mRNA level (Nilsson et al. 2003).…”

Consequences of Intrauterine Growth Restriction for the Kidney

“…ACE inhibition in neonatal rats leads to an increased renal expression of IGFBP-1 [221] , thereby inhibiting IGF-I action. By adding IGF-I to the ACE inhibition, the animals show normalized renal function and histology [23] .…”