title: 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 would affect fetal tubuloglomerular feedback (TGF) under control conditions and after the inhibition of macula densa-derived nitric oxide (NO). Based on previous observations we hypothesized that, the TGF curve of fetuses of subtotally nephrectomized (STNx) ewes would resemble that of a volume expanded fetus with a high production rate of NO and that inhibition of neuronal nitric oxide synthase (nNOS) would increase the sensitivity of the TGF system in these fetuses. Renal function studies were performed on anaesthetized fetal sheep (133-140 days gestation; term ~150 days; Isoflurane 2-4% in oxygen). 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 ewes compared to fetuses of untreated ewes. Interestingly, and contrary to our hypothesis, the fetuses of STNx ewes exhibited no difference in TGF sensitivity in the presence or absence of 7-nitroindazole (7NI; nNOS inhibitor), compared to fetuses of untreated ewes, although sensitivity and reactivity increased in both groups after 7NI. There was however, a decrease in the stop flow pressure and net filtration pressure with an increase in the filtration coefficient (Kf). These factors suggest that maternal renal impairment drives the glomerular hypertrophy which has previously been found to be present in the neonatal period. Thus, we conclude that at ~138 days gestation, the fetal kidney has matured functionally and fetuses of STNx ewes are able to maintain fluid and electrolyte homeostasis even in the presence of increased transplacental flux.
authors.affiliation: Australian School of Advanced Medicine Macquarie University, Sydney, New South Wales, Australia Department of Physiology, School of Medical Sciences University of New South Wales, Sydney, New South Wales, Australia anita.turner@mq.edu.au.
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Turner
authors.affiliation: Department of Physiology, School of Medical Sciences University of New South Wales, Sydney, New South Wales, Australia Department of Medical Cell Biology, Division of Integrative Physiology, University of Uppsala, Uppsala, Sweden.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Brown
authors.affiliation: Department of Physiology, School of Medical Sciences University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Boyce
authors.affiliation: Department of Physiology, School of Medical Sciences University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Gibson
authors.affiliation: Department of Physiology, School of Medical Sciences University of New South Wales, Sydney, New South Wales, Australia Department of Medical Cell Biology, Division of Integrative Physiology, University of Uppsala, Uppsala, Sweden.
authors.forename: A Erik G
authors.initials: AE
authors.lastname: Persson
keywords: 7NI; TGF; micropuncture; nitric oxide; subtotal nephrectomy