Fetal Plasma Arginine Vasopressin Concentrations Research Articles

Intravenous angiotensin induces brain c-fos expression and vasopressin release in the near-term ovine fetus.

The effect of intravenous angiotensin II (ANG II) on fetal brain c-fos expression and arginine vasopressin (AVP) release was studied in the near-term ovine fetus. Fetuses with chronically implanted catheters received an intravenous infusion of ANG II or saline. Fetal plasma AVP concentrations were significantly increased after the peripheral administration of ANG II, with peak levels (3-fold) at 30 min after the intravenous infusion. There was no change in fetal plasma osmolality, sodium, and hematocrit levels between the control and experimental groups or between the periods before and after the infusion of ANG II. Intravenous ANG II administration induced Fos immunoreactivity (Fos-IR) in the circumventricular organs and the median preoptic nucleus of the fetal brain. Fos-IR was also demonstrated in the fetal supraoptic nuclei (SON). Double labeling demonstrated that the AVP-containing neurons in the SON were expressing c-fos in response to intravenous ANG II. These results indicate that the peripheral ANG II in the fetus may play a significant role in stimulating the central hypothalamic-neurohypophysial system during late gestation. It supports the hypothesis that circulating ANG II may act at the fetal AVP neurons in the hypothalamus in body fluid balance via the circumventricular organs, which are situated outside the blood-brain barrier, and the central neural pathway between these two brain structures has been relatively established in utero, at least at near-term.

The ovine fetal endocrine reflex responses to haemorrhage are not mediated by cardiac nerves.

This study was designed to test the hypothesis that cardiac receptors tonically inhibit the secretion of renin, arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) in late-gestation fetal sheep. Eight chronically catheterised fetal sheep between 122 and 134 days gestation were subjected to injection or infusion of saline or 4 % procaine into the pericardial space. Fetal blood pressure and heart rate were monitored and fetal blood samples were drawn to measure the response to these injections. Injection of procaine into the pericardial space effectively blocked cardiac nerves, as evidenced by a reduction in the variability of fetal heart rate and by the blockade of reflex reductions in fetal heart rate after intravenous injection of phenylephrine (an alpha-adrenergic agonist which raises blood pressure). Injection of saline had no discernable effects on any of the measured variables. A single injection of procaine, followed by a slow infusion, produced a transient blockade of cardiac nerves. Multiple injections of procaine produced a sustained blockade of cardiac nerves and a sustained rise in fetal plasma renin activity and ACTH. In none of the experiments did procaine significantly alter fetal plasma AVP concentrations. In 11 fetuses between 121 and 134 days gestation, we combined the cardiac nerve blockade with slow haemorrhage to test the cardiac nerves as mediators of the endocrine response to haemorrhage in utero. Cardiac nerve blockade exaggerated the fetal blood gas response to haemorrhage somewhat but did not significantly alter the magnitude of the ACTH, AVP, or plasma renin activity response to haemorrhage. We conclude that cardiac nerves in the late-gestation fetal sheep have minor influences on plasma renin activity and ACTH in normovolaemic fetuses, but that changes in cardiac nerve activity do not mediate the endocrine responsiveness to haemorrhage.

Role of fetal sac fluids during maternal water deprivation in sheep

Our aim was to determine the importance of amniotic and allantoic fluids for the maintenance of fetal plasma composition during maternal dehydration when water transfer from mother to fetus is likely to be reduced. Eight pregnant ewes were studied before, during and after water deprivation (36 h), firstly with the fetal fluid sacs intact and then with them drained of fluid for 5 days. When water deprivation was combined with drainage, the increases in the osmolalities, [Na+] and [Cl-] in maternal plasma, in fetal plasma and in lung liquid; the increases in fetal urinary osmolality and [Na+]; and the increases in maternal plasma and fetal plasma arginine vasopressin concentrations were greater than those resulting from water deprivation alone. Our results show that during maternal water deprivation, an absence of fluid in the fetal sacs increases both the osmotic stimulus to the fetus and the fetal responses resulting in conservation of water and salt. We conclude that, when the mother is deprived of water, fluid in the fetal sacs is used to limit the degree of maternal and fetal dehydration.

Adenosine mediates hypoxic release of arginine vasopressin in fetal sheep.

The effects of adenosine on plasma arginine vasopressin (AVP) concentrations were determined in chronically catheterized fetal sheep (> 0.8 term). Infusion of adenosine [0.35 +/- 0.01 (SE) mg.min-1.kg-1] into the inferior vena cava of six fetuses caused a transient fall in arterial PO2 (by approximately 3 Torr), a slight reduction in arterial pH, and a 5- to 6-mmHg decrease in diastolic pressure without significantly affecting systolic or mean arterial values. A lower rate of infusion (0.19 +/- 0.01 mg.min-1 x kg-1) in five fetuses had virtually no effect on arterial blood gases, pH, or arterial pressures. Both the low- and high-dose adenosine infusions significantly increased fetal plasma AVP concentrations (1.7 +/- 0.2 to 25 +/- 7 pg/ml and 1.6 +/- 0.1 to 54 +/- 8 pg/ml, respectively). Intravenous infusion of papaverine lowered fetal diastolic and mean arterial pressures by approximately 8 mmHg but had no significant effect on plasma levels of AVP. During an hour of isocapnic hypoxia (arterial PO2 12-13 Torr), fetal plasma AVP levels increased from 1.7 +/- 0.2 to 40 +/- 6 pg/ml. Intra-arterial infusion of the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline significantly blunted the hypoxia-induced rise in plasma AVP concentrations to a maximum mean level of 11 +/- 6 pg/ml. These results indicate that 1) adenosine causes a dose-dependent increase in plasma AVP concentrations and 2) a hypoxia-induced rise in fetal adenosine levels triggers vasopressin release.

Oral-nasal membranes are not the major route for fetal absorption of amniotic fluid arginine vasopressin

Intraamniotically injected substances such as arginine vasopressin and digoxin have been found to rapidly appear in the ovine fetal circulation, irrespective of whether the fetal esophagus has been ligated or occluded. To determine if the ovine fetal oral-nasal membrane plays a significant role in this fetal absorption of amniotic substances, we used two groups of chronically catheterized fetal sheep with a surgical glove sewed over the fetal head to prevent access of the head to amniotic fluid. In the first group 22.5 μg of arginine vasopressin was injected into the amniotic cavity; in the second group 22.5 μg was injected into the glove over the fetal head. We found that, after injection into the amniotic cavity, there were rapid and highly significant increases in amniotic fluid arginine vasopressin concentrations, from 6.1 ± 1.3 to 51 ,249 ± 18,182 pg/ml (mean ± SE) (p < 0.00001). Concurrently there was a rapid increase in fetal plasma arginine vasopressin concentrations from 4.5 ± 1.3 to 93.8 ± 18.9 pg 1 ml (p < 0.00001). The increase was significant within 15 minutes and reached a maximum at 60 minutes after the injection. Fetal arterial pressure increased by 10 ± 2 mm Hg, whereas heart rate decreased by 30 ± 5 beats/min (p < 0.00001 ). In contrast, after the injection into the glove covering the fetal head, there were no significant changes in any of the measured parameters. This suggests that the ovine fetal oral-nasal membrane is not a significant route of absorption of amniotic fluid arginine vasopressin and that the most likely route of absorption is the vascularized fetal surface of the placenta and vascularized fetal membranes, i.e., the intramembranous pathway. (AM J OBSTET GYNECOL 1991;165:1614-20.)

Fetal Arginine Vasopressin under Basal and Hypoosmolal Conditions

Blood samples (4 ml) for plasma arginine vasopressin (AVP) measurements were obtained at 3- to 4-hour intervals under basal conditions for 1-2 days from 5 date-bred ewes with chronic maternal and fetal vascular catheters. In addition, 6 chronically catheterized ewes were infused with 2 liters of 0.45% NaCl over 30 min. Fetal and maternal blood samples were obtained before and after the infusion period for measurement of plasma osmolality and AVP concentrations. In the first study, maternal and fetal plasma AVP levels correlated significantly (p less than 0.01, by linear regression analysis) under basal conditions. In the second study, baseline mean (+/- SEM) plasma osmolality was similar for pregnant ewes and fetuses (303 +/- 3.1 and 302 +/- 2.4 mosm/kg, respectively). There was a significant (each, p less than 0.01 by paired t test) decrease from baseline in maternal and fetal osmolality during the 30 min after completion of the hypotonic saline (to 292 +/- 4.7 and 296 +/- 2.4 mosm/kg, respectively). Fetal plasma AVP levels decreased 17 +/- 6% by 30 min following the completion of water loading (1.7 +/- 0.07 to 1.4 +/- 0.16 microU/ml; p less than 0.05). Maternal plasma AVP levels decreased 16 +/- 4% by 30 min after completion of infusion (1.6 +/- 0.14 to 1.38 +/- 0.6 microU/ml; p less than 0.05). These results indicate that maternal and fetal plasma AVP levels correlate under basal conditions and that maternal water loading, which significantly decreases fetal plasma osmolality, significantly suppresses fetal plasma AVP concentrations.

Mechanism of arginine vasopressin release in the sheep fetus.

Maternal and fetal plasma concentrations of arginine vasopressin (AVP) during asphyxial and hypoxemic episodes were ascertained between 130 and 140 days of gestation in chronically catheterized sheep. During an acute asphyxial stress, i.e., decreased PaO2 and pHa and increased PaCO2, maternal AVP in plasma was unaltered, whereas fetal arterial plasma concentrations rose from 1.6-2.2 microunits/ml to 34-385 microunits/ml and were associated with massive expulsion of meconium into the amniotic fluid. Mild hypoxemia, induced while the mother breathed a gas mixture consisting of 85% nitrogen and 15% oxygen, did not affect either maternal or fetal plasma AVP concentrations. The use of 10% inspired oxygen resulted in 60% and 50% reductions in maternal and fetal PaO2, respectively (P less than 0.05). In this instance, the maternal plasma AVP levels were unchanged, whereas the fetal plasma AVP concentration rose from a mean of 2.61 +/- 0.14 (SE) to 10.2 +/- 2.59 microunits/ml (P less than 0.025) within 30 min. Expulsion of meconium into the amniotic fluid did not occur. No evidence or either fetal-maternal placental transfer or fetal-placental clearance of plasma AVP was obtained. Although hypoxemic stress resulted in an elevation of fetal plasma AVP concentration, it does not appear to be the sole factor responsible for AVP release during intrauterine stress. It is suggested that substantial elevations in fetal plasma AVP concentrations may play in integral role in the fetal expulsion of meconium into the amniotic fluid.