ALTERATIONS IN FETAL URINE PRODUCTION DURING PROLONGED HYPOXEMIA INDUCED BY REDUCED UTERINE BLOOD-FLOW IN SHEEP - MECHANISMS

1. Our aim was to identify mechanisms whereby prolonged fetal hypoxaem ia alters renal function and urine production in fetal sheep. 2. Fetal hypoxaemia was induced for 24 h by reducing uterine blood now at 129. 0 +/- 2.1 days of gestation (term 145-147 days), causing a reduction i n fetal arterial O-2 saturation (SaO(2)) from 52.5 +/- 2.3 to 22.0 +/- 1.3% (P < 0.05). This hypoxaemia was initially associated with a mild acidaemia (pH 7.23 +/- 0.03). 3. The glomerular filtration rate (GFR) increased from a control value of 1.8 +/- 0.3 mL/min per kg to a maxi mal value of 2.8 +/- 0.6 mL/min per kg (P < 0.05) at 4-5 h of hypoxaem ia, returning to control levels by 6-9 h of hypoxaemia. After 4 h of h ypoxaemia renal blood flow was no different to control values (144 +/- 8 mL/min per 100 g kidney weight) but after 24 h of hypoxaemia it had increased to 190 +/- 8 mL/min per 100 g kidney weight (P < 0.05). Fra ctional reabsorption of Na+ in the proximal tubules decreased from a c ontrol value of 81.5 +/- 2.2 to 65.2 +/- 3.9% at 2-3 h of hypoxaemia ( P < 0.05) and remained reduced (68.5 +/- 3.1%) at the end of hypoxaemi a (P < 0.05). Fetal mean arterial pressure transiently increased (P < 0.05) but returned to control values by 4-5 h of hypoxaemia. Fetal ren al vascular resistance was not significantly altered during hypoxaemia . Fetal urine production increased from a control value of 12.3 +/- 2. 1 mL/h per kg to a maximal value of 19.1 +/- 4.2 mL/h per kg at 4-5 h of hypoxaemia (P < 0.05) and returned to control by 24 h of hypoxaemia . 4. Our results indicate that prolonged fetal hypoxaemia leads to the inhibition of Na+ reabsorption in the proximal portion of the renal t ubules. Changes in GFR induced by hypoxaemia were similar to those in fetal urine production and were not associated with changes in renal b lood flow. We conclude that prolonged fetal hypoxaemia affects renal h aemodynamics and the reabsorptive capacity of the renal tubules, resul ting in a diuresis.