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.
Highlights
Maternal renal insufficiency in pregnancy is known to be associated with prematurity, intrauterine growth restriction and risk of fetal loss (Alexopoulos et al 1996; Trevisan et al 2004) along with the risk of an accelerated deterioration of the maternal renal disease (Zacur and Mitch 1977; MacCarthy and Pollak 1981; Cunningham et al 1990; Holley et al 1996; Jungers et al 1997)
STNx ewes were heavier than untreated ewes (65.4 Æ 1.4 kg, n = 16 vs. 56.8 Æ 2.3 kg, n = 14; P < 0.01), and their mean arterial pressure (MAP) was higher (74.9 Æ 3.8 mmHg vs. 60.9 Æ 2.9 mmHg; P < 0.05) but there was no difference in heart rate
PCO2 was higher in STNx ewes compared to untreated ewes (35.2 Æ 1.8 mmHg vs. 28.5 Æ 1.3 mmHg, P < 0.01), but there was no difference between the groups in arterial PO2 or pH
Summary
Maternal renal insufficiency in pregnancy is known to be associated with prematurity, intrauterine growth restriction and risk of fetal loss (Alexopoulos et al 1996; Trevisan et al 2004) along with the risk of an accelerated deterioration of the maternal renal disease (Zacur and Mitch 1977; MacCarthy and Pollak 1981; Cunningham et al 1990; Holley et al 1996; Jungers et al 1997). Given that chronic renal disease is often asymptomatic, it is possible that many women become pregnant under conditions of subclinical renal insufficiency; the effect of this on fetal kidney development is the focus of the current study. Our laboratory has developed an ovine model of chronic maternal renal insufficiency (subtotal nephrectomy, STNx) that produces subclinical signs (Gibson et al 2006). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
