Temporal relationships among fetal urine flow, ANF, and AVP responses to hypertonic infusions

The fetal urine flow response to acute increases in osmolality may be mediated by changes in the plasma concentrations of atrial natriuretic factor (ANF), arginine vasopressin (AVP), and/or angiotensin II (ANG II). To explore this, hypertonic NaCl or mannitol was infused intravascularly over 10 min into chronically catheterized fetal sheep and their mothers simultaneously, followed by a 2-h maternal infusion at 1-2 ml/min to maintain the elevated osmolality. Fetal osmolality rose by 16 mosmol/kgH₂O during 13% mannitol and 2.5% NaCl infusions and by 57 mosmol/kgH₂O during 7% NaCl infusions. Large increases in fetal urine flow occurred in the three groups with peak flows (average of 304%, P < 10^-6) at 0-4 min after the end of the infusion. Flow declined to preinfusion values in all groups at 30-40 min. These changes in urine flow occurred in parallel with a rise (to 223%, P < 10^-6) and fall in plasma ANF concentrations. One hour after the infusions, urine flow declined to 50% of control concomitant with elevations in plasma AVP (to 414%, P < 10^-6), whereas plasma ANG II concentration did not change. Thus the initial increase in fetal urine flow in response to acute hypertonic infusions is temporally related to a rise in fetal plasma ANF, whereas the subsequent fall in urine flow is temporally related to a fall in plasma ANF and a simultaneous rise in AVP concentration. This suggests that ANF may contribute to the acute urine flow increase after hypertonic infusion, whereas AVP appears to be more important for the long-term regulation of fetal urine flow.