Fetal tubuloglomerular feedback in an ovine model of mild maternal renal disease

Abstract

Fetuses of pregnant ewes, which were subtotally nephrectomized prior to mating,were studied to assess whether mild maternal renal impairment wouldaffect fetal tubuloglomerular feedback (TGF) under control conditions andafter the inhibition of macula densa-derived nitric oxide (NO). Based onprevious observations we hypothesized that, the TGF curve of fetuses of subtotallynephrectomized (STNx) ewes would resemble that of a volumeexpanded fetus with a high production rate of NO and that inhibition of neuronalnitric oxide synthase (nNOS) would increase the sensitivity of the TGFsystem in these fetuses. Renal function studies were performed on anaesthetizedfetal sheep (133–140 days gestation; term ~150 days; Isoflurane 2–4% inoxygen). Fetuses were removed from the uterus and placed in a water bath(39.5°C) while maintaining umbilical blood flow. Glomerular filtration rate(GFR) and urine flow rate were markedly increased in fetuses of STNx ewescompared to fetuses of untreated ewes. Interestingly, and contrary to ourhypothesis, the fetuses of STNx ewes exhibited no difference in TGF sensitivityin the presence or absence of 7-nitroindazole (7NI; nNOS inhibitor), comparedto fetuses of untreated ewes, although sensitivity and reactivity increasedin both groups after 7NI. There was however, a decrease in the stop flow pressureand net filtration pressure with an increase in the filtration coefficient(Kf). These factors suggest that maternal renal impairment drives the glomerularhypertrophy which has previously been found to be present in the neonatalperiod. Thus, we conclude that at ~138 days gestation, the fetal kidney hasmatured functionally and fetuses of STNx ewes are able to maintain fluid andelectrolyte homeostasis even in the presence of increased transplacental flux.