Fetal Plasma Sodium Research Articles

Prenatal water deprivation alters brain angiotensin system and dipsogenic changes in the offspring

Objective: Central renin–angiotensin system (RAS) plays an important role in regulating body fluid balance. The present study determined the effect of maternal dehydration on brain expression levels of angiotensinogen, angiotensin II receptor subtypes, and dipsogenic responses in offspring. Methods: Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined. Results: Maternal water deprivation significantly decreased fetal body and brain weight, and body and tail length. Fetal plasma sodium, osmolality, and hematocrit were increased. Both AT1R and AT2R protein abundance was significantly increased in the fetal brain, associating with increased mRNA levels of AT1aR and AT2R. Additionally, angiotensinogen mRNA was increased. In adult offspring, prenatal dehydration resulted in significant increases in AT1R protein and AT1aR mRNA, as well as angiotensinogen mRNA in the forebrain in both males and females. In contrast, AT2R mRNA and protein were increased only in males. Prenatal dehydration resulted in a significant increase in intracerebroventricular angiotensin II-induced water intake in male, but not female, offspring. Conclusion: The results provided new information that antenatal water deprivation induces a reprogramming of brain RAS and Ang II receptor expression patterns and alters the central Ang II-mediated dipsogenic response in offspring in a sex-dependent manner.

Metabolic effects of ritodrine hydrochloride in the pregnant sheep.

The effects of ritodrine hydrochloride on maternal and fetal arterial blood pH and pCO2, plasma electrolytes and maternal plasma glucose and free fatty acid levels were investigated in the third-trimester pregnant sheep. Ritodrine produced a slight fall in the maternal and fetal arterial pH without changes in the arterial pC02. The pH values were, however, within a normal range. Increases in the maternal plasma glucose and free fatty acid levels were also observed. Although maternal and fetal plasma sodium and chloride concentrations did not change, the potassium decreased in a dose-dependent manner both in the ewe and in the fetus following sequential ritodrine infusion. Constant infusion of ritodrine (3 mcg/kg/min), which is a sufficient dose to inhibit uterine contractions, also resulted in a significant decrease in the maternal plasma potassium concentration. It appears to be necessary to give attention to the metabolic effects of ritodrine in long-term therapy of premature labor.

Prenatal dehydration alters renin–angiotensin system associated with angiotensin-increased blood pressure in young offspring

The renin-angiotensin system (RAS) has an important role in cardiovascular homeostasis. This study determined the influence of water deprivation during pregnancy on the development of the RAS in rats, and examined blood pressure (BP) in the adolescent offspring. Pregnant rats were water deprived for 3 days at late gestation, and we examined fetal cardiac ultrastructure, as well as heart angiotensin (Ang) II receptor protein and mRNA, liver angiotensinogen and plasma Ang II concentrations. We also tested cardiovascular responses to i.v. Ang II in the young offspring. In utero exposure to maternal water deprivation significantly decreased fetal body and heart weight, and increased fetal plasma sodium and osmolality. Fetal liver angiotensinogen mRNA, plasma Ang I and Ang II concentrations were also increased. Although fetal AT(1a) and AT(1b) receptor mRNA and AT(1) protein were not changed, AT(2) receptor mRNA and protein levels in the heart were significantly increased following maternal dehydration. Prenatal exposure to maternal water deprivation had no effect on baseline BP; however, it significantly increased BP in response to i.v. Ang II infusion, and decreased baroreflex sensitivity in the offspring. In addition, the heart AT(2) receptor mRNA and protein were higher in the offspring exposed to prenatal dehydration. The results of this study demonstrate that prenatal dehydration affected the RAS development associated with an Ang II-increased BP in fetal origin.

Interactions between maternal subtotal nephrectomy and salt: effects on renal function and the composition of plasma in the late gestation sheep fetus

Effects of altered maternal salt intake between 122 and 127 days gestation (term is 150 days) were studied in eight fetuses carried by ewes which had renal insufficiency caused by subtotal nephrectomy (STNxF) and seven fetuses carried by intact ewes (IntF). Plasma sodium and osmolality were increased in ewes with subtotal nephrectomy on a high-salt intake (0.17 m NaCl in place of drinking water for 5 days; P < 0.05). The STNxF had normal body weights. A high maternal salt intake did not affect fetal blood pressure or heart rate. Plasma osmolality was higher in STNxF (P < 0.001), and plasma sodium and osmolality were increased by high salt (P < 0.001 and P < 0.04, respectively). The STNxF had higher urinary osmolalities (P = 0.002), which were also increased by a high maternal salt intake (P = 0.03). Renal blood flow fell in STNxF in response to a high maternal salt intake, but increased in IntF (P = 0.003). In STNxF but not IntF, glomerular filtration rate and urinary protein excretion were positively related to fetal plasma renin levels (P < or = 0.01). It is concluded that the salt intake of pregnant ewes with renal insufficiency affects maternal and fetal osmolar balance, fetal plasma sodium and fetal renal function. Since STNxF also had altered renal haemodynamic responses to high maternal salt and evidence of renin-dependent glomerular filtration and protein excretion, we suggest that interactions between dietary salt and pre-existing maternal renal disease impair glomerular integrity and function in the fetus.

Maternal 1-deamino-8- d-arginine-vasopressin–induced sequential decreases in plasma sodium concentration: Ovine fetal renal responses

Objective: Acute maternal plasma hypotonicity induces a reduced placental osmotic gradient that contributes to augmented maternal-to-fetal water flow. Subsequently, maternal plasma hyponatremia results in fetal plasma hyponatremia, increased fetal urinary flow, and ultimately increased amniotic fluid volume. We hypothesized that both the degree of reduction in the placental osmotic gradient and the degree of fetal plasma hyponatremia influence fetal urinary diuretic responses. To differentiate the roles of these factors, we determined fetal urinary responses to graded levels of plasma hyponatremia during a constant placental osmotic gradient. Furthermore, we sought to establish the minimum level of plasma hyponatremia necessary to facilitate an increase in fetal urine production. Study Design: Seven pregnant ewes (130 ± 2 days) were prepared with maternal and fetal vascular catheters and a fetal bladder catheter. After 6 days of recovery, fetal urinary flow and urine and plasma compositions were measured during a 2-hour control period. At 2 hours, tap water (2 L, 38°C) with a 20-g bolus of 1-deamino-8- d-arginine-vasopressin was administered to the ewe. Maternal plasma sodium concentration was decreased from control by 5 to 7, 10 to 12, and 15 to 17 mEq/L, and held at each level (levels 1, 2, and 3) for 60 minutes. Results: 1-Deamino-8- d-arginine-vasopressin administration induced sequential decreases in maternal and fetal plasma sodium concentrations (control 146.9 ± 0.5 mEq/L and 141.0 ± 0.5 mEq/L, respectively) at level 1 (140.1 ± 0.6 mEq/L and 136.7 ± 0.7 mEq/L, respectively), level 2 (132.5 ± 0.7 mEq/L and 130.6 ± 1.1 mEq/L, respectively), and level 3 (125.4 ± 1.2 mEq/L and 123.0 ± 1.5 mEq/L, respectively). The maternal-fetal placental osmolality and sodium gradients were constant at each hypotonicity level. Fetal urinary flow significantly increased in association with the degree of hyponatremia (from 0.17 ± 0.03 mL/kg/min to 0. 26 ± 0.04 mL/kg/min, 0.33 ± 0.05 mL/kg/min, and 0.38 ± 00.5 mL/kg/min at levels 1, 2, and 3, respectively). Conclusions: These results indicate the following: (1) Sequential decreases in maternal plasma tonicity result in parallel decreases in fetal plasma tonicity. (2) The fetal urinary diuretic response is highly correlated with the degree of fetal plasma hypotonicity, despite a constant placental osmotic gradient. A fetal therapeutic response (53% increase in fetal urine production) may be induced by a maternal plasma sodium concentration decrease of only 5 to 7 mEq/L. (Am J Obstet Gynecol 1999;180:82-90.)

Regulation of hypothalamic arginine vasopressin messenger ribonucleic acid and pituitary arginine vasopressin content in fetal sheep: Effects of acute tonicity alterations and fetal maturation

Objective: Fetal arginine vasopressin contributes to fetal and amniotic fluid homeostasis by increasing water resorption in the kidney and, at higher plasma levels, circulatory homeostasis by vasopressor effects. In utero and neonatal exposure of rat pups to prolonged alterations in plasma osmolality may permanently alter (imprint) pituitary arginine vasopressin content and adult responses to osmotic challenges. Our objective was to investigate fetal developmental changes and the impact of maternal dehydration and maternal hyponatremia on fetal pituitary arginine vasopressin content and hypothalamic arginine vasopressin messenger ribonucleic acid expression. Study Design: Ten pregnant ewes with singleton fetuses (135 ± 1 day) were chronically prepared with maternal vascular catheters. Ewes were assigned to receive water deprivation (n = 4) [desamino, d -Arg8]-arginine vasopressin–induced plasma hyponatremia (n = 3), or 4 days of observation (n = 3). Three additional pregnant ewes with preterm (110 ± 1 day) singleton fetuses were also included for a study of maturational effects. Daily maternal blood samples were analyzed for determination of plasma arginine vasopressin, electrolytes, and osmolality. After the study protocol, fetuses were operatively delivered, umbilical blood samples obtained, and fetuses put to death for pituitary and hypothalamic tissues. Pituitary arginine vasopressin content was determined by radioimmunoassay, and hypothalamus arginine vasopressin messenger ribonucleic acid expression was detected by Northern blotting. Results: Dehydration significantly (P < .05) increased, and hyponatremia significantly decreased maternal plasma sodium concentration compared with controls. Fetal plasma sodium concentration significantly changed in parallel with maternal values (dehydration: 139 ± 1 to 150 ± 1 mEq/L; hyponatremia: 138 ± 1 to 128 ± 5 mEq/L). Fetal hypothalamic arginine vasopressin messenger ribonucleic acid expression and pituitary content did not change in relation to these relatively acute alterations in plasma tonicity. However, among all animals, arginine vasopressin messenger ribonucleic acid expression was significantly negatively correlated with pituitary arginine vasopressin content (r2 = 0.563; P = .02). Arginine vasopressin messenger ribonucleic acid expression was significantly lower in both preterm and near-term fetuses (P < .05) than that in the maternal ewe, although pituitary arginine vasopressin content (in micrograms per milligram of protein) was significantly greater in preterm fetuses (P < .01, vs maternal; P < .05, vs near term). Conclusions: The significant inverse relation between arginine vasopressin content and arginine vasopressin messenger ribonucleic acid suggests a dynamic arginine vasopressin synthesis–content feedback relationship is functional in the near-term fetus. Although relatively acute periods of maternal hypertonicity or hypotonicity do not alter fetal pituitary arginine vasopressin content or hypothalamic arginine vasopressin messenger ribonucleic acid expression, longer-term plasma tonicity alterations may potentially have an impact on the fetal arginine vasopressin hypothalamic-pituitary axis. (Am J Obstet Gynecol 1998;179:899-905.)

Fetal electrolyte and acid-base responses to amnioinfusion: lactated Ringer's versus normal saline in the ovine fetus.

We hypothesized that amnioinfusion with normal saline would increase fetal plasma sodium and chloride concentrations, resulting in a hyperchloremic acidosis, and that these alterations would not occur after amnioinfusion with lactated Ringer's solution. Chronically catheterized fetal sheep (137 +/- 1 days' gestation; mean +/- SE) were divided into three groups: control (n = 8), infused with normal saline (n = 10), and infused with lactated Ringer's solution (n = 10). The protocol consisted of a 30-minute pre-infusion period, a 1-hour amnioinfusion, and a 1-hour recovery period. During amnioinfusion, warmed solution was infused at a rate of 100 mL/minute for 1 hour. Fetal plasma and amniotic fluid electrolyte concentrations and osmolalities were measured every 20 minutes. Statistical analysis was by analysis of variance and linear regression. Amniotic fluid electrolyte concentrations changed significantly (P < .001) in both amnioinfusion groups, resulting in amniotic fluid compositions that were essentially the same as the infused fluid 20 minutes after starting the amnioinfusion. Significant increases in fetal plasma Na+ and CI- concentrations (2-3 mEq/L) occurred in the normal-saline infusion group relative to both the control and lactated Ringer's groups (P < .001). The lactated Ringer's group demonstrated only a modest increase in plasma Na+ (P = .04) and no change in plasma Cl- concentration. Fetal arterial pH decreased (-0.015 U) in the normal-saline group, and the change in fetal pH was linearly related to the change in plasma Cl- concentration (r = -0.532, P = .004). Normal-saline amnioinfusion can significantly alter fetal plasma electrolyte concentrations and blood pH, whereas amnioinfusion with lactated Ringer's solution results in minimal changes in fetal electrolytes and acid-base balance. The fetal plasma changes that occur during saline infusion are in the physiologic but not the pathologic range.

Ovine fetal swallowing and behavioral state responses to sublingual water.

Ovine fetal swallowing primarily occurs in bouts of activity associated with low voltage electrocorticogram activity and breathing movements. Despite similar rates of electromyographic swallowing activity, there are significant differences in the net esophageal fluid flow among fetuses. To determine if variations in the volume of fluids accessible to the fetus (amniotic fluid, lung fluid, salivary secretions) affect fetal swallowing, we studied the effects of sublingual distilled water infusions on ovine fetal swallowing rates and esophageal flow. Seven pregnant ewes at 127 +/- 2 days gestation were chronically instrumented with maternal and fetal vascular catheters, fetal electrocortical, electro-ocular and electromyograph electrodes, an esophageal flow probe and a sublingual infusion catheter. Following a 2-hour control period, consecutive sublingual infusions of room temperature distilled water (10 and 20 ml/kg/h) were administered for 2 h each. In response to sublingual infusions, fetal plasma sodium (142.5 +/- 0.5 to 140.8 +/- 0.8 mEq/l), chloride concentrations (109.2 +/- 0.4 to 107.7 +/- 0.7 mEq/l) and osmolality (302 +/- 2 to 298 +/- 2 mOsm/kg) decreased significantly. Swallowing activity and esophageal flow did not change significantly from basal values (47 +/- 9 swallows/h, 19.2 +/- 4.2 ml/h) during the sublingual infusions. However, fetal low-voltage electrocortical activity increased significantly during both infusion periods (42 +/- 3 to 56 +/- 6%). Sublingual distilled water infusion decreases fetal plasma osmolality and alters fetal behavioral state without affecting swallowing frequency or esophageal flow.

Effect of a hypertonic saline load on plasma concentrations of atrial natriuretic peptide in fetal calves and their dams

Plasma concentrations of atrial natriuretic peptide (ANP) were studied in eight adult non-pregnant cows and in two groups of six chronically catheterized bovine fetuses and their mothers in the eighth month of pregnancy. The first group of fetuses was used for studying the effect of an acute i.v. sodium load (240 mmol NaCl/fetus) on fetal ANP; the second group acted as controls. The mean basal ANP levels in the third-trimester bovine fetus were three to four times higher than maternal values (39.5 +/- 5.5 and 9.4 +/- 0.6 pmol/l respectively; P less than 0.01). Basal maternal plasma ANP levels were twice as high in pregnant cows in the third trimester of pregnancy than in non-pregnant cows (9.4 +/- 0.6 and 4.3 +/- 0.7 pmol/l respectively; P less than 0.05). In response to an i.v. hypertonic saline injection, fetal plasma ANP levels increased significantly (P less than 0.01) to a maximum of 86.7 +/- 17.6 pmol/l 10 min after the injection, and returned to baseline within 60 min after the treatment; during the 20 min following the i.v. sodium load, fetal plasma ANP correlated significantly with fetal plasma sodium concentrations (r = 0.96; n = 12) and with fetal plasma osmolality (r = 0.94; n = 12). No significant changes in maternal ANP values were observed in the two groups of animals. These results suggest that ANP secretion is stimulated during pregnancy in cows, and that, in the bovine fetus, a hypertonic sodium load appears to be a potent stimulus for ANP release.

Effect of maternal intravenous infusions on fetal extracellular fluid composition in pregnant ewes.

Infusion of intravenous solutions to women in labor is common clinical practice. Since these infusions may change the volume and electrolyte balance between the mother and fetus, we investigated the influence of acute maternal volume expansion upon fetal and maternal fluid and electrolyte equilibrium in the chronically catheterized fetal lamb. Paired measurements of maternal and fetal plasma sodium and potassium concentrations, osmolality, and colloid osmotic pressure (COP), plus measurements in the fetal-placental plasma volume were obtained following rapid maternal infusions with saline, dextrose, and dextran solutions. Maternal infusions resulted in changes in fetal electrolyte concentrations as well as alterations in transplacental COP differences. Despite these changes, however, no changes in fetal plasma volume were noted.

Changes in fetal renal function in response to infusions of a hyperosmotic solution of mannitol to the ewe.

In six pregnant ewes a reduction in transplacental water transfer was produced by increasing maternal osmolality (by infusion of 180 g of mannitol in 500 ml of 0.15 M-sodium chloride) and the fetal renal responses to this reduction in water transfer were studied. These responses were compared with the renal responses of five other chronically catheterized fetal lambs whose mothers received I.V. infusions of 500 ml of 0.15 M-sodium chloride. Intravenous infusion of 500 ml of 0.15 M-sodium chloride to the ewe produced no changes in fetal plasma sodium, potassium or plasma renin activity and had no effect on fetal renal function. After I.V. infusion of mannitol to the ewe, fetal urinary flow rate fell from control levels of 0.69 +/- 0.12 ml/min to 0.32 +/- 0.04 ml/min (S.E. of mean, P less than 0.006). This fall in urinary flow rate was due to increased water reabsorption because there was no change in glomerular filtration rate and osmolar clearance. Fetal urinary sodium excretion increased from 16.2 +/- 2.0 mumol/min, to 34.2 +/- 6.9 mumol/min (S.E. of mean, P less than 0.04). This increase in fetal urinary sodium excretion was due to a fall in the fractional reabsorption of sodium which was related to this rise in fetal plasma sodium levels that occurred following infusion of mannitol to the ewe. The increases in fetal plasma sodium levels were also associated with reductions in fetal plasma renin activity.

Maternal fetal osmolar homeostasis: fetal posterior pituitary autonomy.

Summary: After the infusion of a bolus of 225 mEq NaCl (HS) to maternal ewes, we studied fetal plasma sodium, osmolality, total serum solids, plasma arginine vasopressin (AVP) and plasma renin activity (PRA) responses in 16 chronically catheterized, 112–139 days of gestation fetal lambs. To examine the degree to which this might have represented transplacental passage of AVP, we infused a large amount of synthetic AVP into the fetal circulation (protocol 3) and detected no change in maternal plasma AVP. The protocol was designed to allow multiple, frequent blood sampling not possible by infusing the synthetic AVP into the maternal circulation. In order to compare the fetal AVP response elicited by HS in the maternal ewe and that after direct HS into the newborn lamb and fetus, we calculated stimulus response ratio (SRR) as: Log (AVP)1 - Log (AVP)2, divided by Δosmolality. The SRR of lamb fetuses after maternal HS was significantly greater (0.16 ± 0.02) than that after direct fetal HS (0.04 ± 0.01). In comparison, the newborn lamb has a SRR of 0.02 ± 0.01, and the ewe has a SRR of 0.02 ± 0.01 after HS. These data suggest that after maternal HS infusion, both a volume and, to a lesser extent, an osmolar stimulus for AVP secretion occurs after an induced water flux from the fetal to maternal compartments. Maternal plasma sodium concentration rose promptly from a base line of 146 ± 2.2 (mean ± SEM) to 157 ± 2.8 mEq/liter by 1–20 min where it remained throughout the hour observation period. Fetal plasma sodium concentration rose more slowly from base line of 143 ± 1.8 to 149 ± 1.8 mEq/liter by 1 hr. When 85 mCi22Na was additionally infused with the HS, fetal 22Na constituted only 10% of maternal 22Na counts by the end of 1 hr. During the same period fetal PRA rose from a base line of 12.9 ± 3.8 to 32.0 ± 3.6 ng/ml/hr, while maternal renin remained unchanged. Maternal AVP rose modestly, 11 min after the HS, but promptly returned to base line. There was a rapid and sustained rise by fetal AVP from a base line of 0.7 μU/ml to a peak of 8.2 μU/ml by 22 min post HS. A fetal SRR, Log (AVP)1-Log (AVP)2/Δosmolality after maternal HS was greater than that after direct fetal HS or HS to the ewe or newborn lamb. In an additional experiment, using five chronically catheterized fetuses, 10 million μU AVP injected in the fetal circulation failed to produce an increase in maternal AVP. These results demonstrate that: 1) AVP does not cross the placenta; 2) the fetal sheep neurohypophysis is autonomous and responsive to both direct and indirect (maternal) osmolar stimulation; and 3) the relatively slow rate of maternal to fetal sodium transfer, the augmented SRR after maternal HS, and the elevated fetal PRA and AVP concentration suggest that there is a rapid fetal to maternal flow of water after maternal HS and a combined volume and osmolar stimulus to the fetus. Speculation: Infusions of hypertonic saline in pregnant ewes resulted in rapid increases of fetal plasma sodium due to transfer of water from fetus to mother. A marked rise in fetal renin activity and AVP was also observed. The increase in AVP exceeded that seen in the mother and that produced by infusing hypertonic saline in the fetus. Fetal secretion of AVP is stimulated by hyperosmolality and volume contraction. Elevated AVP may help the fetal kidney retain water and, thereby, minimize hypotonic urine formation and volume depletion.

Bidirectional sodium fluxes across the placenta of conscious sheep.

Conscious pregnant sheep in the last 3 wk of gestation were studied 1--3 days after surgery. Fetal plasma sodium concentration was significantly lower than maternal. A mean electrical potential difference (PD) of 34 +/- 4 (SE) mV (n = 24) was recorded between maternal and fetal intravascular catheters, the mother being positive with reference to fetus. Unidirectional fetomaternal (Jf leads to m) and maternofetal (Jm leads to f) sodium fluxes were determined by application of Fick's principle to uterine and umbilical circulations following injection of 22NaCl or 24NaCl to fetus or mother, respectively. Blood flows were measured by an antipyrine technique. Jm leads to f = 0.142 +/- 0.029 mmol/min (n = 10); Jf leads to m =0.137 +/- 0.015 mmol/min (n = 21). Jm leads to f increased as a linear function of calculated fetal weight. In seven sheep both Jm leads to f and Jf leads to m were measured in a single experiment. The measured ratio Jm leads to f/Jf leads to m was significantly different from the ratio predicted using Ussing's flux ratio equation. There is probably a transplacental sodium pump active in the direction fetus to mother.

CONFIGURATION OF THE FETAL ELECTROCARDIOGRAM IN RELATION TO FETAL ACID‐BASE BALANCE AND PLASMA ELECTROLYTES

SummaryThe configuration and time constants of the fetal electrocardiogram have been analyzed in relation to maternal and fetal acid‐base status and plasma electrolytes in 102 cases in which the fetus was considered to be “at risk”.Computer analysis of the results showed that fetal acidosis is associated with prolongation of electrical systole (QT) and with T‐wave inversion, and that these changes became better defined at the time of delivery. Similar changes were seen in relation to fetal hyperkalaemia. A comparison of scalp blood pH and corrected QT times has shown that scalp blood pH provides the more reliable method for prediction of fetal condition at birth.Maternal plasma sodium and potassium concentrations showed a highly significant positive linear correlation with fetal plasma sodium and potassium concentrations. Fetal plasma potassium levels showed a significant negative relationship with fetal blood pH and standard bicarbonate values. In the presence of fetal acidosis the ratio of fetal to maternal plasma potassium concentration increases, and hence a gradient for potassium loss from the fetus develops.