Renal blood flow and micropuncture studies were conducted in late gestation fetal sheep (gestational age 134 - 141 days; term 150 days) and neonatal lambs (8 - 18 days after birth) to study the forces involved in glomerular filtration (GFR) and characterize the tubuloglomerular feedback (TGF) system during development. These studies required the kidney to be immobilized so stable models in acutely prepared anaesthetized animals were developed. Fetuses were studied in a heated water bath exteriorized from the uterus but with an intact umbilical circulation. The lower GFR in fetuses than lambs was found to be due to both lower net filtration pressures (P<0.001) and a lower ultrafiltration coefficient (P<0.001). TGF was present at both ages, but in fetuses the sensitivity was higher (P<0.001) and reactivity was lower (P<0.001). The reduction in TGF sensitivity between fetal and neonatal life may facilitate the increase in renal blood flow and GFR which occurs at this time. In both fetuses and lambs the sensitivity of the TGF curve was reduced by volume expansion (P<0.001, P<0.05) and reactivity was reduced in lambs (P<0.001). Furosemide abolished TGF at both ages. In both fetuses and lambs, TGF reactivity was increased by inhibition of neuronal nitric oxide synthase (nNOS; P<0.01, P<0.001) and in lambs, TGF sensitivity was increased (P<0.01). This indicates that nitric oxide produced by the macula densa modulates TGF during development. In offspring destined to become hypertensive due to maternal dexamethasone treatment in early gestation TGF sensitivity tended to be enhanced in fetal life and was enhanced in lambs (P<0.01). Increased TGF sensitivity may contribute to the development of hypertension in this model of developmental programming. The effects of nNOS inhibition were attenuated in these animals, suggesting that they have low tonic production of nitric oxide by the macula densa. In fetuses whose mothers had been subtotally nephrectomized prior to mating to induce maternal mild renal impairment, GFR was increased (P<0.01) but net filtration pressure was reduced (P<0.001) so the ultrafiltration coefficient was increased (P<0.001). TGF sensitivity was normal and the effects of nNOS inhibition were similar to normal fetuses.
| Identifer | oai:union.ndltd.org:ADTP/229998 |
| Date | January 2008 |
| Creators | Turner, Anita Jillian, Medical Sciences, Faculty of Medicine, UNSW |
| Publisher | Publisher:University of New South Wales. Medical Sciences |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://unsworks.unsw.edu.au/copyright, http://unsworks.unsw.edu.au/copyright |
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