Urea production and arginine metabolism are reduced in the growth restricted ovine foetus

Abstract

Urea production may be impaired in intrauterine growth restriction (IUGR), increasing the risk of toxic hyperammonaemia after birth. Arginine supplementation stimulates urea production, but its effects in IUGR are unknown. We aimed to determine the effects of IUGR and arginine supplementation on urea production and arginine metabolism in the ovine foetus. Pregnant ewes and their foetuses were catheterised at 110 days of gestation and randomly assigned to control or IUGR groups. IUGR was induced by placental embolisation. At days 120 and 126 of gestation, foetal urea production was determined from [C-14]-urea kinetics and arginine metabolism was determined from the appearance of radioactive metabolites from [H-3]-arginine, both at baseline and in response to arginine or an isonitrogenous mixed amino acid supplementation. Urea production decreased with gestational age in the embolised animals (13.9 +/- 3.1 to 11.2 +/- 3.0 mu mol/kg per min, P <= 0.05) but not in the controls (13.3 +/- 3.5 to 14.8 +/- 6.0 mu mol/kg per min). Arginine supplementation increased urea production in both groups, but only at 126 days of gestation (control: 15.0 +/- 8.5 to 17.0 +/- 9.4 mu mol/kg per min; embolised: 11.7 +/- 3.1 to 14.3 +/- 3.1 mu mol/kg per min, P <= 0.05). Embolisation reduced foetal arginine concentrations by 20% (P <= 0.05) while foetal arginine consumption was reduced by 27% (P <= 0.05). The proportions of plasma citrulline and hydroxyproline derived from arginine were reduced in the embolised animals. These data suggest that foetal urea production and arginine metabolism are perturbed in late gestation after placental embolisation.