Regulation of urine osmolality in fetal sheep

Urine osmolality was measured daily from day of cannulation (80-110 d) until term in six chronically cannulated ovine fetuses. Fetal urine was hypertonic to plasma following surgery, and 24-36 h before parturition. On fifty-five occasions plasma antidiuretic hormone (ADH) concentration was measured concurrently with urine osmolality. When fetal urine osmolality was 154 +/- 45 mosmol/kg water, plasma ADH was 5.6 +/- 2.1 pg/ml (mean +/- S.D.; n = 33) in fetuses less than 120 d gestation. In ten samples from fetuses from 121 d to term urine osmolality was 118 +/- 35 mosmol/kg water when the concurrent plasma ADH concentration was 5.5 +/- 2.1 pg/ml. Urine osmolality greater than 300 mosmol/Kg water was associated with endogenous plasma ADH concentrations of 6.2-9.2 pg/ml in fetuses 86 d until term. However, when exogenous synthetic arginine vasopressin (AVP) was infused into non-stressed fetuses with initial urine osmolalities less than 200 mosmol/Kg water, the minimum plasma ADH concentration that had to be established in order to induce the production of a hypertonic urine was 22.1 pg/ml at gestational ages 95-105 d, 11-1 pg/ml at 110-120 d and 7 pg/ml at 121-130 d. The fetal kidney thus becomes more responsive to infused AVP over the last half of gestation. Under conditions of in utero stress, however, hypertonic urine can be produced at lower endogenous plasma ADH concentrations than required to be established by infusion in non-stressed fetuses, suggesting that urinary concentrating mechanisms independent of ADH are established in these fetuses.