Fetal Plasma Arginine Vasopressin Research Articles

Central angiotensin I increases fetal AVP neuron activity and pressor responses

Angiotensin (Ang) II plays a critical role in cardiovascular homeostasis and neuroendocrine regulation. Little is known about whether central angiotensin-converting enzyme (ACE) is functional in the fetal brain. We investigated cardiovascular and neuroendocrinological responses to intracerebroventricular (icv) application of Ang I in the chronically prepared near-term ovine fetus in utero and examined the action sites marked by c-fos expression in the fetal hypothalamus. ACE mRNA was detected in the specific central areas. Intracerebroventricular Ang I significantly increased fetal blood pressure and c-fos expression in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) in the hypothalamus, accompanied by an increase of fetal plasma arginine vasopressin (AVP). Double labeling demonstrated that AVP neurons in the fetal SON and PVN were expressing c-fos. Captopril, an inhibitor of ACE, significantly suppressed fetal pressor responses and plasma AVP. Double labeling experiments showed colocalization of AT(1) receptor (AT(1)R) and c-fos expression in both SON and PVN following icv Ang I. The results indicate that central endogenous ACE has been functional at least at the last third of gestation and the endogenous brain renin-angiotensin system-mediated pressor responses and AVP release via AT(1)Rs by acting at the sites consistent with the cardiovascular network in the hypothalamus.

Central cholinergic signal-mediated neuroendocrine regulation of vasopressin and oxytocin in ovine fetuses

BackgroundThe hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli. It is well established that central cholinergic mechanisms are critical in the regulation of cardiovascular responses and maintenance of body fluid homeostasis in adults. Our recent study demonstrated that intracerebroventricular (i.c.v.) injection of carbachol elicited an increase of blood pressure in the near-term ovine fetuses. However, in utero development of brain cholinergic mechanisms in the regulation of the hypothalamic neuropeptides is largely unknown. This study investigated AVP and OT neural activation in the fetal hypothalamus induced by central carbachol.ResultsChronically prepared near-term ovine fetuses (0.9 gestation) received an i.c.v. carbachol (3 μg/kg). Fetal blood samples were collected for AVP and OT assay, and brains were used for c-fos mapping studies. I.c.v. carbachol significantly increased fetal plasma AVP and OT concentrations. Intense FOS immunoreactivity (FOS-ir) was observed in the fetal supraoptic nuclei (SON) and paraventricular nuclei (PVN) in the hypothalamus. Double labeling demonstrated that a number of AVP- and OT-containing neurons in the fetal SON and PVN were expressing c-fos in response to central carbachol.ConclusionThe results indicate that the central cholinergic mechanism is established and functional in the regulation of the hypothalamic neuropeptides during the final trimester of pregnancy. This provides evidence for a functional link between the development of central cholinergic mechanisms and hypothalamic neuropeptide systems in the fetus.

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.

Osmotic threshold and sensitivity for vasopressin release and fos expression by hypertonic NaCl in ovine fetus.

In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 +/- 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.

Evidence for mechanisms of the acute-phase response to endotoxin in late-gestation fetal goats

OBJECTIVE: The aim of this study was to evaluate the relationship between febrile response to fetal endotoxin administration and fetal plasma endogenous pyrogen, tumor necrosis factor-α, the possible putative pyrogen mediator prostaglandin E 2, and the endogenous antipyretic arginine vasopressin in late-gestation pregnant goats. STUDY DESIGN: Changes in fetal core temperature, plasma tumor necrosis factor-α, prostaglandin E 2, and arginine vasopressin levels were measured after administration of Escherichia coli endotoxin (70 μg/kg of fetal weight) to 10 fetal goats in late gestation. RESULTS: Fetal body temperature did not rise after endotoxin administration. Fetal plasma tumor necrosis factor-α and arginine vasopressin increased to 87.5 ± 15.2 pg/mL and 25.1 ± 4.8 pg/mL, respectively, after 1 to 2 hours ( P < .05). Fetal plasma prostaglandin E 2 levels did not change significantly throughout the study. CONCLUSION: The absence of a febrile response to endotoxin in late-gestation fetal goats is accompanied by a deficient responses in prostaglandin generation in the periphery and increased activity of the antipyrogen arginine vasopressin. (Am J Obstet Gynecol 1998;179:750-5.)

Arginine Vasopressin-Induced Changes in Blood Flow to the Ovine Chorion, Amnion, and Placenta Across Gestation

To determine whether physiological increases in fetal plasma arginine vasopressin (AVP) concentration alter blood flow rates to the ovine chorion, amnion or placenta, and to determine whether these AVP-induced changes in flow are dependent on gestational age. Colored microspheres (15.10 +/- 0.02 microns (standard deviation) were infused into the superior vena cava before and at 30, 75, and 125 minutes of an intravenous AVP infusion (3 ng/min/kg) in 9 chronically catheterized fetal sheep between 103 days to 141 days gestation (term = 147 days). Chorion, amnion, and placental cotyledons were removed, and microspheres were counted to determine blood flow rates. Fetal arterial pressure (FAP) increased (analysis of variance, P < .0001) and heart rate (FHR) decreased (P < .0001) during the infusion, with responses greater in older (> 125 days) compared to younger (< 125 days) fetuses (P < .001). Chorionic blood flow rate increased by 19 +/- 7% at 30 min of the AVP infusion, and declined by 18 +/- 6% at 75 min, and 32 +/- 5% at 125 min (P < .0001). Similarly, fetal placental blood flow rate increased by 20 +/- 7% at 30 min of infusion, and declined, in parallel with chorionic blood flow rates, by 6 +/- 4% at 75 min, and 17 +/- 4% at 125 min (P < .0001). Amniotic blood flow rate did not change significantly during the infusion. The membranous and placental blood flow rate responses to AVP infusion did not depend upon gestational age. Physiologic increases in plasma AVP concentration induce an early increase in chorionic blood flow followed by a gradual decrease which parallels similar changes in placental blood flow rate. Unlike FAP and FHR, these blood flow changes are not gestational age-dependent. AVP-induced blood flow changes could play an important role in determining abnormalities of amniotic fluid volume observed clinically in some stressed fetuses.

Intraamniotic deamino(D-Arg 8)-vasopressin: Prolonged effects on ovine fetal urine flow and swallowing

OBJECTIVE: Fetal urine is the main source of amniotic fluid, and alterations in urine production have an impact on amniotic fluid dynamics. Intraamniotic arginine vasopressin is absorbed into fetal plasma, but fetal antidiuretic responses may be obscured by vasoconstrictor (V 1 receptor) actions of arginine vasopressin. We determined the effects of intraamniotic administration of a specific V 2 receptor agonist, deamino(D-Arg 8)-vasopressin, on fetal plasma arginine vasopressin immunoreactivity, fetal urine output, and swallowing. STUDY DESIGN: Six chronically prepared pregnant ewes (129 ± 1 days' gestation) received a single deamino(D-Arg 8) (50 μg injection into the amniotic fluid with subsequent measurement of fetal plasma arginine vasopressin immunoreactivity, fetal urine flow and osmolality, and fetal swallowing. RESULTS: Within 30 minutes of deamino(D-Arg 8)-vasopressin administration, fetal plasma arginine vasopressin immunoreactivity (4.5 ± 0.5 to 76.4 ± 21.9 pg/ml) and urine osmolality (135 ± 13 to 285 ± 43 mOsm/kg H 2O) significantly increased and urine flow decreased (0.18 ± 0.01 to 0.05 ± 0.01 ml/kg per minute). After 48 hours urine flow remained reduced (0.08 ± 0.03 ml/kg per minute) and osmolality remained elevated (399 ± 18 mOsm/kg H 2 O). There were no changes in fetal swallowing, systolic (64 ± 3 mm Hg) or diastolic (42 ± 3 mm Hg) blood pressure, or heart rate (169 ± 6 beats/min). CONCLUSION: Intraamniotic deamino(D-Arg 8)-vasopressin administration evokes persistent fetal antidiuresis in the absence of arginine vasopressin - induced fetal cardiovascular effects or changes in fetal swallowed volume, indicating its suitability as a potential therapeutic agent in amniotic fluid volume disorders such as polyhydramnios. (A M J O BSTET G YNECOL 1996;174:78-84.)

Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production

Our aim was to examine the endocrine changes associated with alterations in fetal urine production during 24 h of hypoxemia induced by either reduced uterine blood flow (RUBF) or maternal N2 inhalation (N2). In contrast to RUBF, which caused a diuresis, N2 caused a transient antidiuresis; during both posthypoxemia periods (RUBF and N2), fetal urine production was increased. RUBF, but not N2, was associated with a transient acidemia. Fetal plasma arginine vasopressin (AVP) and atrial natriuretic factor (ANF) concentrations increased during RUBF and were inversely correlated to pH; there were no detectable AVP or ANF responses to N2. Fetal prostaglandin E2 (PGE2) increased during the hypoxemia and posthypoxemia periods induced by both methods, but RUBF caused the greater increase. AVP and PGE2 concentrations were positively correlated with urine production. Fetal arterial blood pressure increased during RUBF but not N2. During RUBF, the increases in AVP and PGE2 concentrations and/or fetal arterial blood pressure may have contributed to the diuresis. During N2, we suggest that low, but increased, levels of AVP may have caused the transient antidiuresis, whereas the diuresis observed during both posthypoxemia periods may have been mediated by elevated PGE2 concentrations and/or increased fetal arterial blood pressure.

Central angiotensin II stimulation of ovine fetal swallowing.

In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation.

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.

Effects of inhibition of prostaglandin synthesis on flow and composition of fetal urine, lung liquid, and swallowed fluid in sheep

Objective: Our aim was to determine the effects of blocking prostaglandin synthesis, by infusion of indomethacin into the fetal circulation, on factors regulating amniotic fluid volume and on plasma composition in the mother and fetus. Study Design: Indomethacin was administered to fetal sheep during 8 hours at 124.0 ± E 1.2 days of gestation (n = 7) and at 134.7 ± 0.8 days of gestation (n = 7) (term ∼ 147 days). Vehicle infusions were performed at 128.8 ± 1.4 days of gestation (n = 5). Results: Fetal urine production was significantly reduced and both fetal urine osmolality and plasma arginine vasopressin concentrations were significantly elevated in response to indomethacin infusions at both gestational ages. Fetal blood and urine lactate concentrations were elevated in response to indomethacin. Later in gestation, fetal lung liquid flow was significantly changed from a net efflux to a net influx. There was no significant effect of indomethacin on the volume of fluid swallowed by the fetus. Conclusion: Inhibition of fetal prostaglandin synthesis profoundly reduces the production of the two major fetal fluids contributing to amniotic fluid, namely, urine and lung liquid. These findings may explain why indomethacin reduces amniotic fluid volume. Objective: Our aim was to determine the effects of blocking prostaglandin synthesis, by infusion of indomethacin into the fetal circulation, on factors regulating amniotic fluid volume and on plasma composition in the mother and fetus. Study Design: Indomethacin was administered to fetal sheep during 8 hours at 124.0 ± E 1.2 days of gestation (n = 7) and at 134.7 ± 0.8 days of gestation (n = 7) (term ∼ 147 days). Vehicle infusions were performed at 128.8 ± 1.4 days of gestation (n = 5). Results: Fetal urine production was significantly reduced and both fetal urine osmolality and plasma arginine vasopressin concentrations were significantly elevated in response to indomethacin infusions at both gestational ages. Fetal blood and urine lactate concentrations were elevated in response to indomethacin. Later in gestation, fetal lung liquid flow was significantly changed from a net efflux to a net influx. There was no significant effect of indomethacin on the volume of fluid swallowed by the fetus. Conclusion: Inhibition of fetal prostaglandin synthesis profoundly reduces the production of the two major fetal fluids contributing to amniotic fluid, namely, urine and lung liquid. These findings may explain why indomethacin reduces amniotic fluid volume.

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.

Effects of inhibition of prostaglandin synthesis on flow and composition of fetal urine, lung liquid, and swallowed fluid in sheep

OBJECTIVE: Our aim was to determine the effects of blocking prostaglandin synthesis, by infusion of indomethacin into the fetal circulation, on factors regulating amniotic fluid volume and on plasma composition in the mother and fetus. STUDY DESIGN: Indomethacin was administered to fetal sheep during 8 hours at 124.0 ± 1.2 days of gestation (n = 7) and at 134.7 ± 0.8 days of gestation (n = 7) (term f147 days). Vehicle infusions were performed at 128.8 ± 1.4 days of gestation (n = 5). RESULTS: Fetal urine production was significantly reduced and both fetal urine osmolality and plasma arginine vasopressin concentrations were significantly elevated in response to indomethacin infusions at both gestational ages. Fetal blood and urine lactate concentrations were elevated in response to indomethacin. Later in gestation, fetal lung liquid flow was significantly changed from a net efflux to a net influx. There was no significant effect of indomethacin on the volume of fluid swallowed by the fetus. CONCLUSION: Inhibition of fetal prostaglandin synthesis profoundly reduces the production of the two major fetal fluids contributing to amniotic fluid, namely, urine and lung liquid. These findings may explain why indomethacin reduces amniotic fluid volume. (AM J OBSTET GYNECOL 1994;170:186-95.)

The adrenocorticotropic hormone and arginine vasopressin responses to hypercapnia in fetal and maternal sheep.

Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.

Maternal/fetal dehydration: prolonged effects and responses to oral rehydration

Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration.

Ovine maternal and fetal renal vasopressin receptor response to maternal dehydration

OBJECTIVE: Arginine vasopressin secretion increases in response to increased plasma osmolality or hypovolemia. Dehydration-induced increases in plasma arginine vasopressin levels have been shown to down-regulate arginine vasopressin V2 receptors in adult rat kidneys. Our study determined ovine maternal and fetal renal arginine vasopressin receptor characteristics and receptor response to maternal dehydration.STUDY DESIGN: Eight pregnant ewes (113 ± 1 days) were dehydrated for 72 hours; eight animals served as controls. Renal medullary tissue was isolated from maternal and fetal kidneys, and arginine vasopressin receptor characteristics determined with saturation and competition assays using tritiated arginine vasopressin, arginine vasopressin, and arginine vasopressin analogs.RESULTS: Euhydrated maternal and fetal renal medullary arginine vasopressin receptor dissociation constant (3.0 ± 0.3 and 1.9 ± 0.3 nmol/L) and maximal binding capacity (149 ± 15 and 111 ± 33 fmol/mg protein) values were similar. Pharmacologic profiles with selective agonists indicated a predominance of V2 receptors. Dehydration significantly increased maternal and fetal plasma osmolalities (304 ± 2 to 320 ± 2; 296 ± 1 to 319 ± 3 mOsm/kg water, respectively) and arginine vasopressin levels (3.8 ± 1.4 to 29.3 ± 4.6; 4.4 ± 1.0 to 16.9 ± 5.0 pg/ml, respectively) but had no effect on arginine vasopressin receptor binding.CONCLUSION: Specific, saturable, single-site tritiated arginine vasopressin binding is present in ovine maternal and fetal renal medullary membranes. Ovine maternal and fetal renal arginine vasopressin receptors do not down-regulate in response to dehydration-induced elevations in plasma arginine vasopressin levels. (AM J OBSTET GYNECOL 1992;167;1717-22.)

Indomethacin-induced urinary flow rate reduction in the ovine fetus is associated with reduced free water clearance and elevated plasma arginine vasopressin levels

OBJECTIVE: The purpose of our study was to explore the urinary responses of the ovine fetus to indomethacin levels comparable with those used therapeutically in the human fetus.STUDY DESIGN: After a 1-hour control period, chronically catheterized ovine fetuses between 125 and 139 days of gestation were given an intravenous bolus of indomethacin (0.05 mg/kg estimated fetal weight) followed by a 0.0025 mg/kg/min continuous infusion for 5 hours. The experimental group (n = 9) was compared with a vehicle-only infusion group (n = 10).RESULTS: There was a sustained 55.7% ± 9.5% (mean ± SEM) decrease in urinary output by 2 hours of indomethacin infusion (p \\lt 0.00001, analysis of variance). Urinary osmolality, potassium, and chloride concentrations underwent sustained increases during the infusion period (p \\lt 0.005). Free water clearance decreased by 67.5% ± 12.0% (p \\lt 0.001). Fetal arterial pressure increased only transiently (p \\lt 0.05), and increases in venous pressure (p = 0.013) and heart rate (p \\lt 0.0001) were sustained. Fetal plasma arginine vasopressin concentration increased during indomethacin infusion (p \\lt 0.05) and was correlated with the fall in urinary flow rate and free water clearance (p = 0.002). During vehicle infusion no significant changes were observed in any of the variables.CONCLUSIONS: Our data indicate that the fetus undergoes antidiuresis when exposed to low levels of indomethacin and that the observed antidiuresis is mediated by a decrease in free water clearance. The reduction in free water clearance may be mediated by increases in plasma arginine vasopressin concentrations. (AM J OBSTET GYNECOL 1992;167:1723-31.)

Concentration thresholds for fetal swallowing and vasopressin secretion.

In adults, plasma osmolality thresholds for hypernatremia-induced arginine vasopressin (AVP) secretion are similar or less than thresholds for stimulation of thirst. In the fetus, the thresholds for swallowing stimulation and AVP secretion have not been defined. Fetal swallowing and AVP secretory responses to hypertonic NaCl and urea were determined in six fetuses (130 +/- 1 1 days) chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyograms (EMG), an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15, 0.30, 0.45, 0.60, 0.75, and 0.90 M), administered at 2-min intervals. A swallow was defined as a coordinated time-sequence of fetal thyrohyoid, nuchal esophagus, and thoracic esophagus EMG activity. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) after four of five injections at each dose. During a 2-h control period swallowing averaged 25.0 +/- 10.1 ml/h and 39.4 +/- 14.6 swallows/h. The mean NaCl threshold concentration for swallowing stimulation was 0.56 +/- 0.06 M. Fetal plasma AVP (2.6 +/- 0.9 pg/ml) increased significantly at the maximum subthreshold (7.6 +/- 4.0 pg/ml) and the threshold NaCl concentration (8.2 +/- 4.0 pg/ml) that stimulated swallowing. On a subsequent day, equiosmolar urea injections increased plasma AVP (from 2.2 +/- 0.7 to 7.6 +/- 2.6 pg/ml) but had no effect on swallowing activity. Fetal mean arterial blood pressure increased after injections of threshold saline and urea concentrations. Fetal arterial blood osmolality and sodium concentration did not change during any study.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraruminal rehydration of ovine fetuses

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.