Persistent changes within the intrinsic kidney-associated NPY system and tubular function by litter size reduction

Background. Intrauterine growth restriction (IUGR) is associated with an increased risk of renal diseases in adulthood. However, while low-birth-weight-infants often undergo accelerated postnatal growth, the impact of postnatal environmental factors such as nutrition and early postnatal stressors on renal development and function remains unclear. In this context, Neuropeptide Y (NPY) may act as a critical factor. NPY is a sympathetic coneurotransmitter involved in blood pressure regulation and tubular function. Yet, little is known about the expression and function of endogenous NPY in the kidney and the functional relevance for the transmission of persistent postnatal-induced effects. Methods. (1) IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. (2) Litter size was reduced to 6 (LSR6) or 10 (LSR10) male neonates. To differentiate the effect of postnatal nutrition and stressors, we additionally included home-cage-control animals without any postnatal manipulation. Animals were sacrificed at Day 70. Results. Litter size reduction (LSR) to 6 but not IUGR increased messenger RNA expression of endogenous NPY and down-regulated the NPY-receptors Y1 and Y2. Furthermore, dipeptidylpeptidase IV (DPPIV)-an enzyme that cleaves NPY-was decreased after LSR. Expression and the phosphorylation of mitogen-activated protein kinase 42/44 (intracellular signalling pathway of the receptor Y1) were altered. An impaired renal function with pronounced kaliuresis and natriuresis was observed at Day 70 after LSR. Conclusions. Postnatal nutrition and stressors such as LSR lead to dysregulated signalling of NPY. These data demonstrate that factors in the early postnatal environment exert important changes in the tubular function, which may predispose to corresponding pathology.