Vasoconstrictor-induced secretion of ANP in fetal sheep

Fetal secretion of atrial natriuretic peptide (ANP) increases during volume expansion and hypoxia. It is unknown whether this is associated with alterations in right atrial pressure (RAP) or distension and whether increases in ANP secretion reflect effects of specific vasopressors. To address this we studied fetal sheep (n = 13) at 125-140 days gestation, infusing either angiotensin II (ANG II; 0.023-5.73 μg/min) or the α-agonist phenylephrine (Phen; 0.031-7.64 μg/min) while monitoring mean arterial pressure (MAP), RAP, heart rate, and amniotic sac pressure. Arterial blood was obtained before and at 5 min of infusion to measure ANP, blood gases, and pH; umbilical venous blood was collected to determine placental clearance of ANP. ANG II caused dose-dependent increases in MAP and plasma ANP (P < 0.05), whereas Phen caused dose-dependent increases in MAP, but ANP rose only with the highest dose (40 ± 12%). ΔMAP and ΔRAP were highly correlated for Phen (r = 0.74, P = 0.002) and ANG II (r = 0.90, P < 0.001), but for both agents the increase in ΔRAP was proportionately greater than ΔMAP, and increases in plasma ANP were greater per millimeter mercury rise in RAP than that observed with MAP. Increases in ANP were associated with a dose-dependent rise in hematocrit, suggesting decreases in intravascular volume. There was no fetal placental clearance of ANP. As in adults, ANG II- and α-agonist- induced fetal ANP secretion appears to primarily reflect increases in RAP and thus right atrial distension.