Determinants of fetal and maternal atrial natriuretic peptide concentrations at delivery in man

Summary. Matched maternal venous (MV), umbilical artery (UA) and umbilical vein (UV) concentrations of atrial natriuretic peptide [ANP] were measured in 36 normotensive women at term delivery (23 vaginal, 13 caesarean) and 17 non-pregnant women in the first half of the menstrual cycle. MV [ANP] at caesarean section was similar to that in nonpregnant women, but UA and UV [ANP] were higher ( P <0.01 for both). UA, but not UV, [ANP] was markedly raised after vaginal delivery. Plasma concentrations of aldosteronce[ALD] were measured in 16 of the matched sets of samples. No statistically significant association was found between [ANP] and [ALD] in either maternal or fetal samples. Neither maternal nor fetal [ANP] correlated with serum Na⁺ or osmolality, haematoerit, blood pressure or heart rate.     

Maternal and fetal atrial natriuretic peptide levels at delivery from normal and growth retarded pregnancies.

OBJECTIVE: To determine whether circulating fetal levels of the vasodilator atrial natriuretic peptide (ANP) are reduced in pregnancies complicated by intrauterine growth retardation (IUGR). DESIGN: Prospective observational study. SETTING: University teaching hospital and research laboratory. SUBJECTS: 25 normal singleton pregnancies delivered at term by spontaneous vertex delivery (n = 16) or by elective caesarean section (n = 9), and a series of 14 singleton pregnancies complicated by IUGR. INTERVENTION: Measurement of ANP by radio-immunoassay in maternal venous, umbilical artery, and umbilical vein plasma from a series of normal, and IUGR pregnancies. MAIN OUTCOME MEASURES: Comparison of plasma ANP levels between the three groups; relation between fetal ANP, PO2 and pH. RESULTS: Mode of delivery did not influence either maternal, umbilical artery or umbilical vein plasma ANP levels in normal term singleton pregnancies. Umbilical vein ANP levels were significantly higher in the IUGR group when compared with normal pregnancies at term (mean 66 95%, CI 36-122 vs mean 37, 95% CI 29-47 pg/ml, P = 0.03) and were inversely related to umbilical artery pH (R2 = 65%; P = 0.003). CONCLUSIONS: These data suggest that umbilical vein ANP levels are elevated in pregnancies complicated by IUGR, and rise appropriately in response to the stress of acidosis. In the absence of any receptor or second messenger defect within feto-placental vascular smooth muscle, these data suggest that ANP is not directly implicated in the vascular pathophysiology of IUGR.     

Reduced atrial natriuretic peptide concentrations in premenstrual syndrome

Atrial natriuretic peptide (ANP) concentrations were determined by radioimmunoassay technique in 23 women, 11 women with premenstrual syndrome (PMS) and 12 comparable asymptomatic women. The asymptomatic women showed no change in ANP concentration during the menstrual cycle. In the PMS group ANP levels showed a significant fall in the midluteal phase compared to levels in the follicular phase. Throughout the cycle ANP concentrations were lower in the PMS group than in the comparison group. This difference was statistically significant in the early, mid and late luteal phases of the cycle. The lower ANP concentration in the PMS group in the luteal phases may indicate either a lower plasma volume or a decrease in the total body sodium content or both. These findings are contrary to those expected.     

Reduced atrial natriuretic peptide concentrations in premenstrual syndrome

Summary. Atrial natriuretic peptide (ANP) concentrations were determined by radioimmunoassay technique in 23 women, 11 women with premenstrual syndrome (PMS) and 12 comparable asymptomatic women. The asymptomatic women showed no change in ANP concentration during the menstrual cycle. In the PMS group ANP levels showed a significant fall in the midluteal phase compared to levels in the follicular phase. Throughout the cycle ANP concentrations were lower in the PMS group than in the comparison group. This difference was statistically significant in the early, mid and late luteal phases of the cycle. The lower ANP concentration in the PMS group in the luteal phases may indicate either a lower plasma volume or a decrease in the total body sodium content or both. These findings are contrary to those expected.     

Atrial natriuretic factor maternal and fetal concentrations in severe preeclampsia

There is a reduction in intravascular volume in patients with preeclampsia. Since the secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention, we sought to determine whether circulating maternal plasma atrial natriuretic factor concentrations were lower in patients with preeclampsia compared to normal pregnant women. The level of alpha-human atrial natriuretic factor was measured by a specific radioimmunoassay. Maternal venous concentrations of a alpha-human atrial natriuretic factor were higher in patients with severe preeclampsia (116.12 +/- 13.37 pg/ml) than in normal pregnant women (80.30 +/- 4.02 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher in fetuses born to patients with severe preeclampsia (197.68 +/- 29.10 pg/ml) than normal control subjects (118.00 +/- 12.52 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher than umbilical or maternal venous concentrations. In cases of severe preeclampsia, despite the presumed volume changes, maternal atrial natriuretic factor concentrations are higher than in normal pregnant women. The fetus appears to produce its own atrial natriuretic factor. Umbilical artery atrial natriuretic factor concentrations in fetuses born to preeclamptic mothers are higher than those seen in normal control subjects.     

Perinatal factors influencing atrial natriuretic peptide levels in umbilical arterial plasma at the time of delivery

Little is known about atrial natriuretic peptide metabolism or secretion in the human fetus. The purpose of this study was to determine if both the placenta and umbilical vessels are possible sites of atrial natriuretic peptide metabolism and to evaluate the effects that labor, route of delivery, prolonged pregnancy, preeclampsia, and fetal distress have on umbilical arterial atrial natriuretic peptide levels. We found that plasma atrial natriuretic peptide levels in the umbilical artery are significantly greater than those in the vein (p less than 0.001). Umbilical arterial and umbilical venous atrial natriuretic peptide levels were higher in plasma samples collected immediately at delivery when compared with those obtained 10 minutes later (p less than 0.001). Umbilical arterial atrial natriuretic peptide levels were elevated in pregnancies complicated by preeclampsia and fetal distress (p less than 0.01). Labor, route of delivery, and prolonged pregnancy had no effect on umbilical arterial atrial natriuretic peptide levels. We propose that both the placenta and umbilical vessels contain atrial natriuretic peptide receptors that are involved in the clearance or metabolism of atrial natriuretic peptide. The increased umbilical arterial atrial natriuretic peptide levels present in preeclampsia and fetal distress may reflect an attempt by the fetus to regulate blood flow.     

Fetal atrial measurements before and after delivery: correlation with plasma atrial natriuretic peptide.

Fetal and early neonatal atrial measurements correlating with plasma atrial natriuretic peptide were studied to evaluate the circulatory change before and after delivery in a longitudinal study of 10 normal fetuses from 1 week before until 5 days after delivery. Before delivery, right atrial area value was significantly larger than that of left atrial area; however, there were no significant differences between left and right atrial areas after delivery. Right atrial area value before delivery was significantly larger than those after delivery, whereas the left atrial area did not change before and after delivery. Combined atrial area value before delivery was also larger than those after delivery. Plasma atrial natriuretic peptide values did not change after delivery. These results suggest that the change from fetal to neonatal circulation mainly caused by the pulmonary circulation induces the change of right atrial size before and after delivery.     

Observations on maternal and fetal ferritin concentrations at term

The concentration of serum ferritin was measured in 115 paired maternal and cord specimens obtained from patients delivering at term. There was a significantly lower concentration of ferritin in cord serum when the maternal value was 10 microgram/l or less. The maternal ferritin appeared to be lower in mothers who had three or more previous pregnancies or were socially deprived.     

Peripheral and intracardiac concentrations of atrial natriuretic peptide in patients with heart disease.

To study the relationship between the plasma concentration of the atrial natriuretic peptide (ANP) and heart function and to discern the secretion pathway of ANP, we determined the peripheral plasma concentration of ANP in 18 heart patients and the intracardiac concentration of ANP in six heart patients during cardiac catheterization. All plasma was extracted through a Sep-Pak C18 cartridge by acid alcohol. The concentration of ANP was determined by a sensitive and specific radioimmunoassay method. We found that the plasma ANP concentration (pg/mL) in heart patients (ranging from 12 to 139, mean = 36.1 +/- 28.9) was statistically higher than that in normal adults (ranging from 8 to 20, mean = 12.4 +/- 3.3, n = 16; p less than 0.05). The ANP level in heart patients was inversely correlated with the left ventricular ejection fraction (r = -0.53, p less than 0.05) evaluated by radionuclide angiocardiography. The intracardiac level of ANP was 88 +/- 58 at the superior vena cava, 77 +/- 55 at the inferior vena cava, 124 +/- 68 at the right atrium, 98 +/- 64 at the right ventricle, 107 +/- 58 at the pulmonary artery, 98 +/- 52 at the left ventricle, 109 +/- 73 at the aorta and greater than 351 at the coronary sinus. In conclusion, ANP is mainly secreted via the coronary sinus into the atrial cavity. The peripheral plasma ANP concentration is higher in heart patients. It increases as the left ventricular ejection fraction decreases. Therefore, plasma ANP concentration may be a useful indicator for the assessment of cardiac function.     

Dehydration increases the renal response to atrial natriuretic peptide in fetal sheep.

OBJECTIVE: In sheep, maternal water deprivation results in urinary natriuresis in spite of suppression of plasma atrial natriuretic factor levels. Near-term fetal sheep also have a urinary natriuresis without change in plasma atrial natriuretic factor during maternal dehydration. This study was designed to explore the role of plasma atrial natriuretic factor levels in fetal dehydration-natriuresis. STUDY DESIGN: Eight chronically instrumented preterm (113 +/- 1 days) ovine fetuses received two atrial natriuretic factor infusions (3 and 15 ng/kg/min) in a euhydrated state and after 48 +/- 1 hours of maternal water deprivation. RESULTS: Dehydration significantly increased maternal plasma osmolality (302 +/- 2 to 313 +/- 2 mOsm/kg water), sodium (148.1 +/- 0.8 to 154.3 +/- 0.4 mEq/L), chloride (112.4 +/- 0.6 to 116.8 +/- 0.9 mEq/L), and arginine vasopressin (4.2 +/- 1.2 to 23.0 +/- 4.0 pg/ml) and significantly decreased plasma atrial natriuretic factor (36 +/- 6 to 19 +/- 4 pg/ml) concentrations. Fetal plasma osmolality (296 +/- 1 to 308 +/- 2 mOsm/kg), atrial natriuretic factor (128 +/- 16 to 241 +/- 36 pg/ml), and arginine vasopressin (3.5 +/- 0.8 to 12.3 +/- 4.8 pg/ml) concentrations and urine osmolality (170 +/- 10 to 253 +/- 10 mOsm/kg), osmolar clearance (0.80 +/- 0.02 to 0.14 +/- 0.02 ml/kg/min), and fractional sodium excretion (3.3% +/- 1.7% to 8.5% +/- 2.1%) increased significantly with dehydration, whereas the plasma atrial natriuretic factor clearance decreased from 127 +/- 27 to 63 +/- 10 ml/kg/min. Dehydration had no effect on fetal hematocrit, vascular pressures, glomerular filtration rate, urine flow, or free water clearance. In euhydrated fetuses plasma atrial natriuretic factor increased from 128 +/- 16 to 287 +/- 46 pg/ml with sequential atrial natriuretic factor infusion, and no significant increases were observed in urine flow, fractional sodium excretion, and glomerular filtration rate. In contrast, atrial natriuretic factor infusion to dehydrated fetuses significantly increased urine flow (0.17 +/- 0.03 to 0.32 +/- 0.07 ml/kg/min), osmolar clearance (0.14 +/- 0.02 to 0.28 +/- 0.06 ml/kg/min), and fractional sodium excretion (8.5% +/- 2.1% to 14.8% +/- 4.0%). CONCLUSION: These results demonstrate that in the fetus at 113 days' gestation plasma atrial natriuretic factor levels increase with dehydration, probably a result of decreased plasma atrial natriuretic factor clearance, and the fetal renal responsiveness to atrial natriuretic factor infusion increases during maternal dehydration.     

Detection of C-type natriuretic peptide in fetal circulation

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that plays an important role in the control of blood pressure, renal function and volume homeostasis. In contrast to the atrial natriuretic peptide and brain natriuretic peptide, CNP acts in an autocrine/paracrine fashion and is considered to be the endothelial component of the natriuretic peptide system. CNP has a high expression and tissue-specific regulation in reproductive organs. Using a radio-immunoassy for CNP-22 we measured for the first time CNP in fetal blood. Samples were taken by cordocentesis in a group of fetuses with rhesus isoimmunisation (10.74 +/- 2.81 pg/ml), fetuses with rhesus isoimmunisation after intravascular transfusion (10.03 +/- 4.01 pg/ml) and a group with structural anomalies (12.9 +/- 5.67 pg/ml). A group of healthy fetuses was used as controls (11.64 +/- 4.32 pg/ml). In contrast to ANP, the fetal CNP-plasma concentrations remain stable in the investigated fetal diseases and after volume load during intravascular transfusion. Moreover, fetal CNP-plasma levels are higher than previously measured maternal concentrations in normal pregnancies. Therefore, the fetus expresses CNP independently of the maternal circulation.     

Catechol estrogen concentrations in maternal and umbilical circulation at different modes of delivery

To investigate the role of catechol estrogens in human parturition, these steroids were analyzed in samples from the maternal venous and umbilical venous and arterial plasma at vaginal (n = 28) and abdominal (n = 28) delivery. To ensure the appropriateness of collection of umbilical artery and venous blood samples, progesterone content was also determined. Although there is no significant difference in maternal vein content of catechol estrogens between the two groups, the umbilical venous (p = 0.03) and arterial (p = 0.002) plasma concentrations are significantly higher at vaginal delivery than those measured at abdominal delivery. In view of the present data and the importance of catechol estrogens in prostaglandin synthesis and in potentiating the activity of catecholamines through competitive inhibition of catechol-O-methyltransferase, it is suggested that catechol estrogens may play a role in triggering the events involved in the onset of labor and delivery in humans.