Effects of prostaglandin E2 on renal function and lung liquid dynamics in foetal sheep

1. The aim of the present study was to determine the effects of prolonged prostaglandin E2 (PGE2) administration on the function of the foetal kidneys and lungs in order to gain a greater understanding of the role played by PGE2 in the control of foetal fluid balance. By studying the effects of PGE2 at two gestational ages, we have also been able to examine the influence of age. 2. We studied the effects of 26 h PGE2 infusion on foetal sheep at a mean (+/- SEM) of 120.0 +/- 0.6 (n = 6) and 139.0 +/- 0.8 (n = 4) days of gestation. In both groups, foetal urine production was significantly inhibited throughout the infusion period (P < 0.05). In younger, but not older foetuses, urine production returned to control values within 24 h of ending the infusion (P < 0.05). This PGE2-induced anti-diuresis was associated with foetal hypoxaemia and acidaemia, a reduction in free water clearance and an increase in foetal plasma arginine vasopressin concentrations (P < 0.05). 3. During PGE2 infusions, foetal breathing movements were inhibited, the effect being greater and more sustained in older foetuses (P < 0.05). 4. Infusions of PGE2 led to increased lung liquid production at both ages (P < 0.05); lung liquid volumes were reduced in older foetuses (P < 0.05), but were unchanged in younger foetuses. The reduction in lung liquid volume in older foetuses may have been due to inhibition of foetal breathing. 5. We conclude that increased circulating levels of PGE2 have profound effects on foetal renal and lung function which, if sustained, could compromise foetal lung development and perinatal well-being.