Gestational Length Affects a Change in the Transepithelial Voltage and the rNKCC2 Expression Pattern in the Ascending Thin Limb of Henle's Loop

Abstract

ABSTRACT:To examine whether the functional and morphologic conversion of the neonatal ascending thin limb (ATL) of Henle's loop is related to gestational length, we evaluated the transepithelial voltages (Vts) of ATLs in perinatal mouse, hamster, rabbit, and rat kidneys. In isolated microperfused tubule preparations, Vts of neonatal ATLs were 23.8 Ϯ 1.4 in mouse, 25.7 Ϯ 2.2 in hamster, and 18.2 Ϯ 1.6 mV in rabbit. The influence of gestational length on the Vts and rat Na-K-Cl cotransporter (rNKCC2) expression pattern was also examined in perinatal rats subjected to a prolonged gestation due to either a daily s. M ammalian neonates possess a nearly mature urinediluting ability at birth (1); however, human neonates are unable to produce hypertonic urine at concentrations Ͼ400 mOsmol/kg, and rats are unable to produce hypertonic urine Ͼ600 mOsmol/kg. These observations indicate that the urineconcentrating ability is quite immature at birth (2). A number of researchers have tried to determine why the urineconcentrating ability of neonates does not reach adult levels; however, none have succeeded in explaining this phenomenon.It was first reported in the 19th century that morphologically, neonatal kidneys do not possess inner medullae (3). Subsequently, Kim et al. (4) clarified the subject by reporting that the ATL of Henle's loop of neonatal rats is also morphologically different from that of adults. They reported that the ATL in the neonatal period is very similar to the thick ascending limb (TAL) and that the tubule is replaced by the mature ATL cells after apoptosis and transformation.In an attempt to clarify the urine-concentrating mechanism in the neonatal period, we examined the renal tubular function directly in a series of experiments using in vitro tubule microperfusion technique and measured mRNAs for wellknown transporters and channels in the isolated inner medullary tubules of fetal, neonatal, and adult rat kidney (5). Our results led to a striking new concept regarding the maturating mechanism for the urine concentrating ability of mammalian neonates. We demonstrated that the renal medullary tubule organization of neonatal rats shares a marked similarity to the avian renal medulla. We postulate that the neonatal period is a phase of functional conversion of the urine concentrating mechanism from avian type to the mammalian type.In mammals, a urine-concentrating mechanism that is more dependent on urea than NaCl is the major protective response to a dry environment. In birds, both regulation of glomerular filtration and a urine-concentrating mechanism that is dependent on NaCl play important roles in fluid and electrolyte homeostasis. From the phylogenetic perspective, the urineconcentrating mechanism is unique in that it is only present in the metanephros of birds and mammals. Urine-concentrating ability develops after birth and matures during the weaning period.Changes in the renal medullary tubular transport properties of mature quail (6 -9), neonatal rats, and mature rats were compared in our previo...

Gestational age and risk factors for cardiovascular disease: evidence from the 1958 British birth cohort followed to mid-life

“…Further, pre-term birth may result in changes to organ development. Support for these explanations, in relation to BP, is provided by evidence from animal studies 41 suggesting that variation in gestational age is associated with differences in kidney structure.…”