Cardiovascular and fluid responses to atrial natriuretic factor in sheep fetus

Presently little is known about the effects of atrial natriuretic factor (ANF) in the fetus. In this study we explored the effects of ANF on vascular pressures and fluid dynamics in the chronically catheterized sheep fetuses averaging 133 days gestation (term = 145-150 days). Under resting conditions plasma ANF concentration was positively correlated with fetal heart rate (P < 0.001) and was not correlated with arterial pressure, venous pressure, or plasma osmolality. The weight-normalized fetal urine flow rate correlated positively with ANF concentration (P < 0.01). After a bolus injection of 8 μg/kg of synthetic human ANF into the inferior vena cava, fetal arterial pressure decreased by 2 mmHg and remained at this level for 60 min, venous pressure was unchanged, and heart rate increased transiently by 15 beats/min. Urine flow rate increased to 250% of control 5 min after the injection and returned to control at 20 min even though ANF was four times control levels. Fetal blood volume decreased significantly by 5% within 10 min and remained low for 60 min. This decrease in blood volume was greater than the increase in urine flow. A kinetic analysis revealed that ANF disappearance from the plasma could not be adequately characterized with a single rate constant due to exchange between plasma and interstitial fluid. By use of a two-compartment model the calculated rate constants for transcapillary exchange and plasma clearance averaged 37 and 15 ml·min^-1·kg^-1, respectively, and the estimated rate of endogenous release of ANF was 13 ng·min^-1·kg^-1. In summary, basal plasma ANF concentration in the sheep fetus may be primarily dependent on heart rate and appears to be a determinant of urinary output. Fetal arterial pressure, heart rate, and blood volume were altered following ANF injection, but the changes were relatively small in magnitude. Thus the present study suggests that ANF does not appear to have extensive short-term effects on the fetal cardiovascular system but may be involved in fluid volume regulation.