Hemorrhage-induced reductions in plasma atrial natriuretic factor in the ovine fetus.

To investigate the effects of blood volume reduction on fetal plasma atrial natriuretic factor concentrations, chronically catheterized ovine fetuses at 109 to 138 days' gestation were subjected either to withdrawal of two consecutive blood samples or to a moderate hemorrhage. In fetuses from which two blood samples of 3.5 ml each (approximately 1% of fetal blood volume) were withdrawn under basal conditions at 15- to 30-minute intervals, plasma atrial natriuretic factor concentrations in the second sample decreased by 17 +/- 7 pg/ml from 178 +/- 8 pg/ml in the first sample (p less than 0.02). If the fetal blood removed during the first sample was replaced with an equal volume of maternal blood, plasma atrial natriuretic factor concentrations did not change significantly. In these same samples, plasma arginine vasopressin and angiotensin II concentrations were unchanged between the two samples regardless of whether volume was replaced. In fetuses subjected to hemorrhages of 21% +/- 2% over 10 minutes without blood replacement, plasma atrial natriuretic factor concentration at 1.5 hours after hemorrhage was suppressed by 42 +/- 10 pg/ml from basal level of 139 +/- 9 pg/ml (p less than 0.05). Plasma atrial natriuretic factor returned to control levels by 5.5 hours after hemorrhage as blood volume returned to normal. Thus in the ovine fetus a reduction in blood volume results in a decrease in plasma atrial natriuretic factor concentrations. Also, atrial natriuretic factor appears to be more sensitive to changes in blood volume than other vasoactive hormones studied.     

Ovine fetal lung fluid response to atrial natriuretic factor

The fetal lung is an important site of fluid production and is postulated to serve a regulatory role in fetal fluid balance. To assess the role of atrial natriuretic factor on fetal lung liquid production, we studied the effect of intravenous atrial natriuretic factor infusion on tracheal fluid production in fetal sheep with chronic vascular and tracheal catheters. Ovine fetuses (mean gestation = 130 days +/- 1 day) received successive 40-minute intravenous infusions of increasing doses of synthetic fragment 1-28 atrial natriuretic factor (5, 25, and 100 ng/min.kg-1). In response to the 25 ng/min.kg-1 infusion, fetal tracheal fluid production decreased from 1.2 +/- 0.3 ml/10 min to 0.6 +/- 0.2 ml/10 min (p less than 0.05), and remained suppressed during the 100 ng/min.kg-1 infusion (0.5 +/- 0.2 ml/10 min). There was a significant inverse correlation between tracheal fluid production and fetal plasma atrial natriuretic factor levels (r = -0.61, p less than 0.001). Basal tracheal fluid sodium and potassium concentrations (147 +/- 1 mEq/L and 5 +/- 1 mEq/L) and osmolality (291 +/- 3 mOsm) did not change during the atrial natriuretic factor infusion periods. The observation that atrial natriuretic factor acts to decrease fetal lung fluid production suggests that atrial natriuretic factor may be important in the fetal adaptive response to extrauterine life.     

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.     

Ovine fetal lung fluid response to intravenous saline solution infusion: fetal atrial natriuretic factor effect

The fetal lung, a significant source of in utero fluid production, has been postulated to serve a regulatory role in maintenance of fetal body fluid homeostasis. Whereas the fetus responds to intravascular saline solution infusions with increased urine output, the fetal lung fluid response to this stimulus is unclear. Tracheal fluid output was measured in four chronically catheterized ovine fetuses (mean gestation, 129 +/- 1 days) subjected to successive 40-minute intravenous 0.9% saline solution infusions at rates of 0.5 and 1 ml/min/per kilogram of body weight. Tracheal fluid output decreased significantly (1.7 +/- 0.1 to 1.1 +/- 0.1 ml/10 min, p less than 0.01) during the infusion and returned to basal levels during the recovery period. Lung fluid osmolality and electrolyte concentration did not change. Fetal plasma atrial natriuretic factor increased significantly in response to the saline solution infusion (364 +/- 90 to 790 +/- 286 pg/ml, p less than 0.05) and returned to basal levels during the recovery period. There was a significant inverse correlation between plasma atrial natriuretic factor levels and tracheal fluid output. These results suggest that increased fetal plasma atrial natriuretic factor decreases lung fluid production. Lung fluid does not appear to compensate for fetal body water excess. Rather, lung fluid production appears to promote intrauterine pulmonary growth and to facilitate the transition to the extrauterine environment.     

Fetal hypoxia elevates plasma atrial natriuretic factor concentration

Acute hypoxia in the fetus is associated with a reduction in fetal blood volume. We hypothesized that atrial natriuretic factor in the fetal circulation may be one of the factors that mediate this blood volume decrease. Thus the present study was designed to determine the effects of hypoxia on circulating concentrations of atrial natriuretic factor in fetal sheep and correlate these changes with fetal blood volume. Hypoxia was induced in chronically catheterized sheep fetuses by infusing nitrogen containing CO2 into the trachea of the ewe for 30 minutes. Fetal arterial PO2 decreased by 10.2 +/- 1.3 (SE) mm Hg. Plasma atrial natriuretic factor concentration rose concurrently with the fall in PO2 such that atrial natriuretic factor increased to 565 +/- 196 pg/ml from a basal level of 127 +/- 13 pg/ml (p less than 0.001). Fetal blood volume was reduced by 7.2% +/- 2.1% and was significantly related to changes in atrial natriuretic factor levels (p less than 0.0001). At the termination of hypoxia, PO2 returned to normal levels before plasma concentrations of atrial natriuretic factor fell to baseline values. Therefore fetal hypoxia appears to be a potent stimulus for elevating plasma concentration of atrial natriuretic factor in the fetus, and this rise in atrial natriuretic factor in the circulation may be partially responsible for the reduction in fetal blood volume observed during hypoxia.     

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.     

Fetal plasma and renal responses to ruminal fluid

Amniotic fluid homeostasis is dependent on a balance of fetal fluid production and absorption. The fetal gastrointestinal tract is believed to resorb 500 to 1000 ml of amniotic fluid per day during 7 to 10 bouts of swallowing activity. However, the impact of ruminal fluid on fetal plasma composition and fluid homeostasis is largely unknown. Seven ovine fetuses (120 +/- 1 day) received intraruminal infusions of 0.9% or 3% saline solution on alternate days. In response to successive 40-minute intraruminal infusions of 0.9% saline solution (0.5 and 1.0 ml/kg/min), there was no change from basal levels of fetal plasma osmolality (295.7 +/- 2.9 mosm), plasma arginine vasopressin (1.45 +/- 0.29 pg/ml), urine osmolality (150 +/- 8 mosm), or urine volume (0.49 +/- 0.10 ml/min). In response to the 3% saline solution infusion, significant increases were noted in fetal plasma osmolality (295.4 +/- 3.1 to 302.6 +/- 2.6 mosm), plasma arginine vasopressin (1.77 +/- 0.31 to 4.84 +/- 0.79 pg/ml), and urine osmolality (157 +/- 13 to 342 +/- 25 mosm), whereas fetal urine volume significantly decreased (0.35 +/- 0.05 to 0.15 +/- 0.06 ml/min). These results indicate that hypertonic, but not isotonic, saline solution infusion into the fetal gastrointestinal tract may affect fetal plasma composition and urine production. Under conditions of significant plasma to luminal osmotic gradients, fetal gastrointestinal water and electrolyte transfer may be more rapid than can be compensated by either fetal renal function or placental equilibration.     

Effects of low-dose dopamine therapy in the oliguric patient with preeclampsia

Central hemodynamic and renal responses to low-dose dopamine (1 to 5 micrograms/kg/min) infusion were studied in six oliguric (less than 0.5 ml/kg/hr) patients with severe preeclampsia. Hemodynamic parameters were measured and renal function tests were done before and during therapy. There was a significant rise in urine output from a mean (+/- SD) of 21 +/- 10 to 43 +/- 23 ml/hr, accompanied by a rise in cardiac output from 6.8 +/- 1.8 to 8.0 +/- 2.3 L/min (p less than or equal to 0.05). There were no significant changes in blood pressure, central venous pressure, or pulmonary capillary wedge pressure. The fractional excretion of sodium, negative free water clearance, and osmolar clearance tended to rise during dopamine therapy. No adverse maternal or fetal effects occurred. We conclude that low-dose dopamine produces a significant increase in urine production with resolution of oliguria in severe preeclampsia.     

Plasma endothelin-1 and atrial natriuretic peptide levels during prolonged (24-h) non-acidemic hypoxemia in fetal goats.

OBJECTIVE: The purpose of this study was to investigate the effects of prolonged (24-h) non-acidemic hypoxemia on plasma endothelin-1 and atrial natriuretic peptide (ANP) in fetal goats. METHODS: During continuous infusion of nitrogen into the maternal trachea, fetal plasma endothelin-1 and ANP levels were measured in nine chronically instrumented goat fetuses at 117-129 days' gestation. Endothelin-1 and ANP were measured by radioimmunoassay. RESULTS: Fetal arterial pO(2) decreased significantly from 23.1 +/- 1.0 mmHg (control) to 15.2 +/- 0.9 mmHg during the first 2 h of hypoxemia and to 15.7 +/- 1.1 mmHg at the end of the experimental period of hypoxemia. The plasma endothelin-1 concentration increased from 10.6 +/- 1.9 pg/ml to 20.4 +/- 4.3 pg/ml (p < 0.05) during the first 2 h and was 19.7 +/- 2.4 pg/ml (p < 0.01) at the end of the experimental period. The plasma ANP concentration also increased, from 20.3 +/- 5.5 pg/ml to 23.0 +/- 4.7 pg/ml in the first 2 h and then to 58.0 +/- 8.8 pg/ml (p < 0.05) at the end of the experimental period. There was a significant negative correlation between fetal plasma endothelin-1 and pO(2), but no significant correlation was found between fetal plasma ANP and pO(2). CONCLUSIONS: Prolonged non-acidemic hypoxemia induces a continuous increase in fetal plasma endothelin-1 and ANP levels. Fetal plasma ANP increases time-dependently but endothelin-1 remains constant during hypoxemia.     

Renal effects of ovine fetal arginine vasopressin secretion in response to maternal hyperosmolality

Acute increases in maternal plasma osmolality can increase amniotic fluid osmolality. Amniotic fluid is primarily derived from fetal urine production, and arginine vasopressin infusion can affect both fetal urine production and amniotic fluid osmolality. To assess the effect of short-term changes in maternal osmolality on fetal arginine vasopressin secretion and renal function, six ewes of 126 +/- 1 days' gestation received intravenous infusions of 20% mannitol (500 ml/10 min). In response to mannitol infusion, both maternal and fetal plasma osmolality increased significantly (302 +/- 3 to 326 +/- 2 and 300 +/- 1 to 309 +/- 2 mosm, respectively). Increased fetal plasma and urine arginine vasopressin concentrations were associated with significant increases in fetal urine osmolality (146 +/- 12 to 262 +/- 30 mosm) and sodium concentration (35.8 +/- 2.8 to 76.5 +/- 20 mu Eq/ml), but fetal urine production rates did not change (0.68 +/- 0.11 to 0.62 +/- 0.15 ml/min). These conclusions were reached: Acute increases in maternal osmolality can affect fetal arginine vasopressin secretion; arginine vasopressin-induced increases in fetal urine osmolality may contribute to increased amniotic fluid osmolality in response to maternal hyperosmolality.     

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.     

Plasma levels of atrial natriuretic peptide during normal pregnancy and in pregnancy complicated by hypertension

To clarify a possible role for atrial natriuretic peptide in the pathophysiology of pregnancy complicated by hypertension, we studied plasma levels of atrial natriuretic peptide in 176 pregnant women with or without hypertension. Plasma atrial natriuretic peptide levels in normal pregnant women showed a gradual increase as pregnancy advanced, but the mean (+/- SD) concentrations in women in each trimester (34.8 +/- 14.7 pg/ml in the first trimester, n = 35; 38.7 +/- 12.2 pg/ml in the second trimester, n = 34; and 43.1 +/- 20.0 pg/ml in the third trimester, n = 71) did not differ statistically from the mean plasma atrial natriuretic peptide level in nonpregnant women (38.2 +/- 13.6 pg/ml, n = 44). In contrast, plasma atrial natriuretic peptide levels were elevated in 9 of the 12 women who had hypertension. The mean plasma atrial natriuretic peptide concentration in these patients (162 +/- 95.2 pg/ml) was significantly (p less than 0.01) higher than in normal pregnant women and in nonpregnant controls. On the other hand, 11 pregnant women with proteinuria or edema but without hypertension had normal plasma atrial natriuretic peptide levels. These results suggest that plasma atrial natriuretic peptide levels are normal in women during uncomplicated pregnancy, while the levels are elevated in pregnancy complicated by hypertension. Increased atrial natriuretic peptide secretion in the latter condition may reflect a mechanism of compensation that operates in response to water and sodium retention.     

Maternal plasma hypertonicity is accentuated in the postterm rat

OBJECTIVE: In humans and rats, pregnancy-associated maternal plasma volume expansion and plasma hypotonicity may facilitate maternal-to-fetal water transfer. Although reduced amniotic fluid volume occurs commonly in postterm pregnancy, the mechanisms are unknown. We previously demonstrated a reversal of pregnancy-induced maternal plasma hypotonicity that occurs in the near term (20 days) pregnant rats. We sought to determine whether the relative maternal plasma hypertonicity continues in the postterm period. STUDY DESIGN: Rat gestation (normal, 21 days) was prolonged with subcutaneous progesterone injection. Pregnant rats at gestation, 18 days, 21 days, and 24 days and nonpregnant rats were studied. Maternal and fetal hematocrit levels, plasma osmolality, electrolyte levels, and amniotic fluid volume were determined. In addition, maternal and fetal tissues were analyzed for water and electrolyte content. RESULTS: Compared with term (21days), postterm pregnant rats (24 days) had a significant increase in maternal and fetal plasma osmolality (293.7+/-1.4 mOsm/kg vs 302.8+/-3.7 mOsm/kg and 301.0+/-2.0 mOsm/kg vs 310.3+/-3.2 mOsm/kg, respectively; P<.01) and sodium and chloride concentrations. Conversely, both maternal and fetal hematocrit levels decreased significantly in the postterm period. Postterm rats demonstrated an increased fetal mortality rate (24%) and a significantly reduced amniotic fluid volume (4.2+/-0.6 mL vs 6.6+/-0.6 mL, P<.01). CONCLUSION: These results indicate that the near-term reversal of maternal plasma hypotonicity that has been observed previously is further accentuated in the postterm pregnancy. This continued hypertonicity may induce a fetal-to-maternal water flow and contribute to postterm oligohydramnios and increased fetal morbidity and mortality rates.     

Increase in the plasma levels of the N-terminal and C-terminal portions of the prohormone of atrial natriuretic factor during normal pregnancy

The influence of pregnancy on the circulating concentrations of atrial natriuretic factor, the 28 amino acid carboxy (C)-terminal end of the 126 amino acid atrial natriuretic factor prohormone, and the amino (N)-terminus of the prohormone was studied with three specific radioimmunoassays recognizing: (1) atrial natriuretic factor (i.e., amino acids 99 through 126), (2) the 98 amino acid N-terminus, and (3) amino acids 31 through 67 from the midportion of the N-terminus of the prohormone. Plasma atrial natriuretic factor in normal pregnant women gradually increased as pregnancy progressed, with the mean +/- SEM being 58 +/- 4 pg/ml in the first trimester, 74 +/- 5 pg/ml in the second trimester, and 89 +/- 7 pg/ml in the third trimester. Likewise, proatrial natriuretic factor 31 through 67 increased from 1421 +/- 76 pg/ml (first trimester) to 1509 +/- 84 pg/ml (second trimester) to 1758 +/- 83 pg/ml in the third trimester, whereas the whole N-terminus of the prohormone increased from 1804 +/- 98 pg/ml (first trimester) to 1909 +/- 111 pg/ml (second trimester) to 2160 +/- 79 pg/ml in the third trimester. These results suggest that release of the N-terminus of the prohormone, as well as atrial natriuretic factor, increases with the rise in blood volume associated with a normal pregnancy. The circulating concentrations of both the C-terminus and N-terminus of the atrial natriuretic factor prohormone increased further in the 48 hours after delivery. Because both the C-terminus and N-terminus of the atrial natriuretic factor prohormone contain diuresis-producing peptides, these results suggest that postpartum diuresis may be mediated by these peptides.     

Chronic in utero plasma hyperosmolality alters hypothalamic arginine vasopressin synthesis and pituitary arginine vasopressin content in newborn lambs

OBJECTIVE: Arginine vasopressin is synthesized in the hypothalamus and secreted by the posterior pituitary gland in response to plasma hypertonicity. Previous studies suggest that in utero and neonatal exposure of rat pups to prolonged alterations of plasma osmolality may permanently alter (imprint) arginine vasopressin synthesis and secretion, thus adult responses to osmotic challenges. Little is known, however, of the potential for imprinting of neuroendocrinologic systems in precocial species. In view of the frequent occurrence of altered maternal and fetal plasma tonicity (eg, maternal dehydration, hyperemesis), we sought to determine the effect of prolonged maternal hypertonicity on arginine vasopressin gene expression and pituitary gland content in neonatal sheep. STUDY DESIGN: Pregnant ewes at 119 +/- 3 days of gestation were water restricted to achieve and maintain plasma hypertonicity (10-20 mOsm/kg above baseline level) until normal term delivery. Newborns were provided maternal nursing ad libitum. Within 24 hours after birth, study neonatal lambs (n = 6) and age-matched control neonatal lambs (n = 5) were killed, and the pituitary gland and hypothalamus were removed and frozen immediately. Pituitary arginine vasopressin content was determined by radioimmunoassay, and hypothalamic arginine vasopressin gene expression was quantified with Northern blot. Differences in pituitary arginine vasopressin content and hypothalamic arginine vasopressin gene expression (arginine vasopressin/ beta-actin ratio) between study and control newborn lambs were analyzed by unpaired t test. RESULTS: In response to maternal water restriction, maternal plasma osmolality increased from 307 +/- 0.9 mOsm/kg to 325 +/- 1.3 mOsm/kg, and plasma sodium increased from 147 +/- 1.3 mEq/L to 156 +/- 1.2 mEq/L. The maternal plasma hyperosmolality and hypernatremia were maintained until normal term delivery. At the time of death, study (in utero dehydrated) lambs had higher plasma sodium (150 +/- 0.4 mEq/L vs 146.5 +/- 1.5 mEq/L; P <.05) and chloride (112.8 +/- 1.0 mEq/L vs 108.5 +/- 1.5 mEq/L; P <.05) levels, and lower potassium (4.5 +/- 0.2 mEq/L vs 5.5 +/- 0.3 mEq/L; P <.05) concentrations than control newborn lambs. Both newborn groups had similar plasma osmolality (320.0 +/- 1.3 mOsm/kg vs 318.0 +/- 3.4 mOsm/kg). Total pituitary arginine vasopressin content was significantly greater in the study than in the control newborn lambs (8.3 +/- 2.8 microg vs 1.6 +/- 1.3 microg; P <.05). Conversely, hypothalamic arginine vasopressin messenger RNA levels were lower in the study newborn lambs than in the control newborn lambs (arginine vasopressin/beta-actin ratio: 0.29 +/- 0.01 vs 0.68 +/- 0.15; P <.05). CONCLUSION: Despite the presence of plasma hypernatremia, prolonged elevation of fetal plasma tonicity increases newborn pituitary arginine vasopressin content yet decreases hypothalamic arginine vasopressin gene expression. The present study suggests that prolonged prenatal exposure to plasma hypertonicity may imprint the hypothalamic-pituitary arginine vasopressin regulatory system.     

Fetal absorption of intra-amniotic aldosterone: effects on urine composition.

OBJECTIVES: Amniotic fluid (AF) volume and composition are maintained by a balance of fetal fluid production and resorption. Ovine fetal resorption of peptide hormones (e.g., arginine vasopressin) from the amniotic cavity has been demonstrated, with resultant effects on fetal urine production. The present study was undertaken to determine whether intra-amniotically administered steroid hormones could be absorbed from the amniotic cavity into fetal plasma and whether intra-amniotic aldosterone administration would affect fetal renal sodium and potassium excretion. METHODS: Seven singleton fetuses (132 +/- 2 days) were prepared with bladder, vascular, and amniotic cavity catheters. After a 5-day recovery period, a bolus of aldosterone was injected into the amniotic cavity. Fetuses were monitored for an additional 24 hours during which time maternal, fetal, and AF samples were collected at timed intervals. RESULTS: After intra-amniotic aldosterone injection, AF aldosterone concentrations increased at 30 minutes and remained elevated for 4 hours after the aldosterone bolus. In response to increased AF aldosterone, fetal plasma aldosterone levels significantly increased by 30 minutes, peaked at 1 hour (17 +/- 4 to 758 +/- 160 pg/mL), and remained elevated for a minimum of 4 hours. Fetal urine sodium excretion significantly decreased and potassium excretion increased. Maternal plasma aldosterone levels increased significantly (25 +/- 10 to 401 +/- 56 pg/mL) but to levels below fetal values. Amniotic fluid and fetal and maternal aldosterone concentrations and fetal urine sodium and potassium excretion returned toward basal levels by 24 hours. CONCLUSION: The steroid hormone aldosterone can be absorbed from the amniotic cavity into the fetal circulation and can alter fetal urine electrolyte excretion. These results suggest that the amniotic cavity is a potential route of in utero pharmacologic fetal therapy.     

Transfer of recombinant human granulocyte colony stimulating factor (rhG-CSF) from the maternal to the fetal circulation is not dependent upon a functional G-CSF-receptor.

Administration of granulocyte colony stimulating factor (G-CSF), a haematopoietic growth factor, to pregnant rats increases neutrophil production in the pups. The mechanism for the placental transfer is unknown, but it has been speculated to involve the placental G-CSF receptor (G-CSFR). The purpose of this study was to test that hypothesis. Pregnant mice were treated with a single subcutaneous dose of 50 microg/kg recombinant human G-CSF (rhG-CSF). Mice with an intact G-CSFR ("wild type", WT) and those with a homozygous deletion in the G-CSFR gene (G-CSFR deficient, "knock-out", KO) were studied. At intervals after injection, fetuses were delivered and maternal blood, amniotic fluid (AF) and fetal blood collected. G-CSF concentrations were measured using an enzyme linked immunosorbent assay specific for human G-CSF. Thirty minutes after injection, G-CSF was measurable in the AF (167+/-50 versus 445+/-217 pg/ml, mean+/-sem, WT versus KO) and fetal plasma (774+/-673 versus 427+/-121 pg/ml, WT versus KO). Peak concentrations occurred 2 h after injection in WT dams (572 542+/-41 262 pg/ml) and 4 h in KO dams (616 100+/-96 300 pg/ml). Therefore, in mice, a functional G-CSFR is not essential for the transfer of rhG-CSF from pregnant dams to their fetuses.     

Ovine hourly fetal urine production: relation to fetal electrocortical activity

OBJECTIVE: Ultrasound studies of hourly urine production rate in human fetuses have suggested that a fall in urine production occurs in state 2F (fetal quiet sleep) secondary to a state-dependent decrease in renal blood flow. We sought to ascertain the relationship between fetal hourly urine production rate and behavioral state in the near-term ovine fetus, a model in which urine production and fetal brain activity can be directly measured. METHODS: Six ewes with singleton pregnancies were prepared with vascular and amniotic fluid catheters. Fetuses were prepared with hindlimb vascular catheters, a bladder catheter, and biparietal ECoG electrodes. After at least 5 days of recovery (ga 130 +/- 2 days; term = 145-150 days), each animal was monitored for a 6-h period. Urine production was measured by draining the bladder catheter through a drop counter and fetal ECoG was continuously recorded (sampling rate of 50 Hz). ECoG activity was analyzed using power spectral analysis and periods of active and quiet sleep identified using both signal amplitude and corresponding 85% spectral edge frequency. RESULTS: Basal fetal arterial pH (7.36 +/- 0.01), pO2 (22.0 +/- 1.2 mmHg) and pCO2 (47.0 +/- 1.6 mmHg) and plasma (295 +/- 2 mOsm/kg) and urine (179 +/- 3 mOsm/kg) osmolalities were within normal ranges. Active and quiet sleep comprised 50 +/- 2 and 43 +/- 1% time, respectively. There was no difference in hourly urine production rate in active sleep (21.4 +/- 9.7 ml/h) and quiet sleep (18.8 +/- 7.7 ml/h). CONCLUSIONS: 1) Hourly fetal urine production rate is independent of ECoG activity state in the near-term ovine fetus. 2) Assuming only minor species differences, ultrasound measurement of human fetal hourly urine production rate can be performed without concern for fetal neurobehavioral state changes.     

Plasma atrial natriuretic peptide in patients with chronic renal failure

Plasma atrial natriuretic peptide (ANP) levels were measured in non-dialyzed and dialyzed chronic renal failure (CRF) patients and in normal subjects. Changes in plasma ANP in response to hemodialysis (HD) and to isolated ultrafiltration (UF) were also investigated in dialyzed CRF patients. Plasma ANP levels were significantly higher in 28 non-dialyzed CRF patients than in 27 normal subjects (mean +/- SEM, 174.0 +/- 25.9 vs 25.0 +/- 1.9 pg/ml, p less than 0.001). Plasma ANP levels did not correlate with blood urea nitrogen or serum creatinine, however patients with advanced renal failure (creatinine clearance less than 10 ml/min) with cardiomegaly (cardiothoracic ratio greater than 50%) or hypertension (BP greater than 140/90 mmHg) had significantly higher plasma ANP levels than those who were not. A 6-hour HD significantly decreased the plasma ANP level (423.4 +/- 71.3 to 220.6 +/- 40.0 pg/ml, p less than 0.001) and body weight in 21 dialyzed CRF patients, and the decrement in plasma ANP showed a positive correlation with the decrement in body weight (r = 0.425, p = 0.056). In 8 dialyzed CRF patients, we further performed a 1-hour isolated UF for removal of isoosmotic intravascular fluid without changes in the solute concentrations, followed by a subsequent 5-hour HD. The decrease in plasma ANP during the 1-hour UF period was 68% of the total ANP decrement for the whole 6-hour study. The average plasma ANP level was decreased with 94.6 +/- 42.5 pg/ml/kg/h in the UF period compared to 3.5 +/- 1.4 pg/ml/kg/h in the HD period (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid intramembranous absorption of water infused into the ovine allantoic cavity.

OBJECTIVE: Previously we found that water infused into the ovine amniotic cavity was rapidly absorbed into the fetal circulation through the vascularized fetal membranes and fetal surface of the placenta (i.e., the intramembranous pathway). The purposes of this study were to (1) estimate the conductance of the intramembranous pathway from the allantoic cavity and (2) determine if the conductance is adequate to offset the inflow of urine, which may be up to 500 ml/day in the near-term ovine fetus. STUDY DESIGN: Seven chronically catheterized fetal sheep averaging 132 +/- 2 (+/- SE) days' gestation underwent an infusion of warmed distilled water into the allantoic cavity at 6 ml/min. The infusions were continued until steady states were obtained in allantoic and amniotic fluid and in fetal and maternal blood osmolalities. During the steady state the conductance of the intramembranous pathway was estimated as the ratio of osmotic gradient to infusion rate. RESULTS: The allantoic and amniotic fluid and the fetal and maternal blood osmolalities decreased by 188 +/- 14, 36 +/- 8, 13 +/- 2, and 3 +/- 1 mOsm/kg, respectively, at steady state. From the fetal-allantoic osmolality gradients the conductance of the intramembranous pathway was 1.72 +/- 0.14 or 0.53 +/- 0.08 microliter/min/mm Hg/kg fetal weight. Assuming a similar conductance during the preinfusion period, the next volume movement would equal 0.67 ml/min (965 ml/day). CONCLUSIONS: The conductance of the intramembranous pathway in combination with the normal osmotic gradient is sufficient to remove the large volume of fetal urine that may enter the allantoic cavity each day.