Plasma vasopressin, renin, and catecholamines during nitroprusside-induced maternal and fetal hypotension in sheep

The release of vasopressin, renin, and catecholamines by the fetus during either maternal or fetal hypotension was examined in chronically catheterized fetal lambs. Nitroprusside was infused intravenously for 1 h into seven pregnant ewes (maternal hypotension) or nine fetal lambs (fetal hypotension); the rates were adjusted to achieve a 15 to 30% decrease in mean blood pressure. During maternal hypotension, mean +/- SE vasopressin in maternal plasma increased from 1.2 +/- 0.2 pg.ml-1 to 208 +/- 153 pg.ml-1 and plasma renin activity increased from 1.5 +/- 0.3 ng.ml-1.h-1 to 6.6 +/- 1.6 ng.ml-1.h-1. Fetal vasopressin and plasma renin activity also increased during the same interval from 1.1 +/- 0.3 to 16.9 +/- 7.5 pg.ml-1 and 3.7 +/- 1.1 to 10.5 +/- 2.85 ng.ml-1.h-1, respectively; but no changes were observed in fetal blood pressure, heart rate, or acid base status. During fetal hypotension, mean vasopressin in fetal plasma increased from 4.3 +/- 3.4 pg.ml-1 to 1054 +/- 772 pg.ml-1, plasma renin activity increased from 5.7 +/- 2.2 ng.ml-1 to 22.2 +/- 7.1 ng.ml-1.h-1, and total catecholamines from 174 +/- 58 pg.ml-1 to 810 +/- 416 pg.ml-1. There was no change in fetal heart rate, acid base status, osmolality, or sodium concentration. The fetus became and remained hypertensive for at least 1 h after the end of infusion. This prolonged hypertension was associated with elevated levels of vasopressin and plasma renin activity. Peak vasopressin levels were proportional to the total nitroprusside dose in both the ewe and fetus (maternal r = 0.796, fetus r = 0.870).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal atrial natriuretic factor and arginine vasopressin responses to hyperosmolality and hypervolemia

Atrial natriuretic factor (ANF) is a class of diuretic and natriuretic peptides secreted by mammalian cardiac atria. Although basal plasma ANF levels in the ovine fetus are elevated relative to the adult, fetal secretion of ANF increases in response to intravascular isotonic saline infusion. Recent in vitro and in vivo studies indicate that ANF secretion also may be stimulated by increased plasma osmolality and/or sodium concentration. The present studies were conducted to determine if volume expansion associated with increased plasma osmolality would further augment ANF secretion in the ovine fetus. In response to successive 30-min intravenous infusions of 3% saline at 0.5 and 1.0 ml/kg/min fetal plasma ANF significantly increased from a basal level of 98 +/- 31 pg/ml to a peak of 439 +/- 42 pg/ml (p less than 0.05). During a 30-min postinfusion recovery period, fetal plasma ANF significantly decreased from peak values to 224 +/- 10 pg/ml (p less than 0.05), although remaining above basal levels. Fetal plasma osmolality significantly increased from 300 +/- 2 mosmol to 325 +/- 3 mosmol (p less than 0.05) whereas fetal plasma arginine vasopressin increased from 1.9 +/- 0.4 to 10.9 +/- 7.0 pg/ml (p less than 0.05) at the conclusion of the 3% saline infusion. During the saline infusion a significant increase in fetal heart rate and decrease in fetal hematocrit were noted. Fetal blood pressure and maternal plasma ANF and arginine vasopressin concentrations remained unchanged. Despite the potential stimulatory effects of hyperosmolality, increased plasma arginine vasopressin, and intravascular volume expansion, the increase in fetal plasma ANF in the present study did not exceed that induced by isotonic saline alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recumbent Cranial Diabetes Insipidus

ABSTRACT. A male, aged 16, with chronic Hypernatremia, adipsia, polyphagia, and poikilothermia was studied regarding regulation and secretion of arginine vasopressin. During recumbency at night, low plasma arginine vasopressin levels and increased volumes of dilute urine were found; whereas plasma arginine vasopressin levels and urine osmolalities rose and urine volumes decreased during ambulation in the daytime. Neither a 25% reduction of mean arterial pressure nor hypertonic saline infusion increased plasma arginine vasopressin or urine osmolalities. Treatment with 1-desamino-D-arginine-vasopressin at 6 p.m. and a scheduled fluid intake according to actual body weight eradicated Hypernatremia and hyperosmolality. These data demonstrate a complete loss of arginine vasopressin secretion to osmotic stimulation, a partial defect of arginine vasopressin secretion to non-osmotic stimulation, an abolished response to stimulation of high-pressure-baroreceptors, but an intact responsiveness to stimulation of low-pressure-baroreceptors.     

Recumbent cranial diabetes insipidus. Studies in a patient with adipsia, hypernatremia, poikilothermia and polyphagia

A male, aged 16, with chronic hypernatremia, adipsia, polyphagia, and poikilothermia was studied regarding regulation and secretion of arginine vasopressin. During recumbency at night, low plasma arginine vasopressin levels and increased volumes of dilute urine were found; whereas plasma arginine vasopressin levels and urine osmolalities rose and urine volumes decreased during ambulation in the daytime. Neither a 25% reduction of mean arterial pressure nor hypertonic saline infusion increased plasma arginine vasopressin or urine osmolalities. Treatment with 1-desamino-D-arginine-vasopressin at 6 p.m. and a scheduled fluid intake according to actual body weight eradicated hypernatremia and hyperosmolality. These data demonstrate a complete loss of arginine vasopressin secretion to osmotic stimulation, a partial defect of arginine vasopressin secretion to non-osmotic stimulation, an abolished response to stimulation of high-pressure-baroreceptors, but an intact responsiveness to stimulation of low-pressure-baroreceptors.     

Platelet vasopressin levels in childhood idiopathic nephrotic syndrome

Despite the importance of disturbances in plasma volume in nephrotic patients, the only clinically accepted measurement of this value in common use is plasma renin activity. We assessed the usefulness of plasma vasopressin levels as an index of plasma volume in patients with idiopathic nephrotic syndrome. However, since 80% to 90% of arginine vasopressin circulates bound to platelets, we measured vasopressin levels in platelet-rich and platelet-poor plasma. The nephrotic patients (n = 19) had significantly higher vasopressin levels in platelet-poor and platelet-rich plasma compared with controls (3.2 +/- 0.6 vs 1.0 +/- 0.3 pg/mL, and 10.4 +/- 3.6 vs 3.3 +/- 0.6 pg/mL. respectively). The percent binding of vasopressin to platelets was reduced in nephrotic patients compared with controls (50.2% +/- 6% vs 70.4% +/- 2.9%). The values for platelet-poor vasopressin, but not platelet-rich vasopressin, correlated significantly with the plasma renin activity (r = .83). We conclude that in nephrotic patients, platelet-poor vasopressin levels correlate with plasma renin activity and may provide a useful measure of minute-to-minute vasopressin release in response to changes in plasma volume.     

Renal hemodynamic responses to hypoxemia during development: relationships to circulating vasoactive substances

Chronically catheterized fetal lambs (n = 11, gestational age 111-139 days) and neonatal lambs (n = 20, postnatal age 4-30 days) were studied to explore during development the relationship of renal hemodynamic responses during hypoxemia to plasma epinephrine concentration (E), plasma norepinephrine concentration (NE), plasma arginine vasopressin concentration (AVP), and plasma renin activity (PRA). A low oxygen gas mixture (11.1 +/- 0.1% O2) was administered for 30 min to the pregnant ewe or neonatal lamb to induce hypoxemia with maintenance of normal arterial pCO2 and pH. Arterial blood pressure was recorded continuously and renal blood flow (RBF) was determined by the radiolabeled microsphere technique. Moderate hypoxemia (pO2 16 +/- 2 torr and 33 +/- 6 torr in fetus and neonate, respectively) induced increases in E, NE (measured by radioenzymatic assay), and AVP (measured by radioimmunoassay) in both fetus and neonate. PRA (measured by radioimmunoassay) also increased in response to hypoxemia in neonatal lambs. The change in mean arterial pressure with hypoxemia (delta MAP) was significant in fetuses (delta MAP 8 +/- 14%, p less than 0.05) but not in lambs (delta MAP 1 +/- 10%, p greater than 0.5). Similarly, the change in renal blood flow with hypoxemia (delta RBF) was significant (delta RBF -51 +/- 24%, p less than 0.001) in fetuses but not in neonatal lambs (delta RBF -9 +/- 38%, p greater than 0.1). These results reflected a change in renal vascular resistance with hypoxemia (delta RVR) that was significant in fetal lambs (delta RVR 169 +/- 168%, p less than 0.01) but not in neonatal lambs (delta RVR 51 +/- 180%, p greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasopressin concentration in amniotic fluid as an index of fetal hypoxia: mechanism of release in sheep

Hypoxia is a potent stimulus to the release of vasopressin in fetal sheep and, in turn, plasma concentrations of the hormone correlate inversely with fetal oxygenation. Because the fetal kidney contributes to vasopressin clearance, we propose that measurement of increased amounts of vasopressin in amniotic fluid would be indicative of fetal hypoxia. We therefore measured concentrations of vasopressin in amniotic fluid under resting conditions, during and after fetal hypoxia, and with intravenous and intra-amniotic administration of vasopressin in 15 chronically instrumented fetal lambs 111-141 d gestation. In the resting state mean (+/- SE) vasopressin concentrations in amniotic fluid (1.6 +/- 0.3 pg . ml-1) did not differ from those in maternal (1.4 +/- 0.4 pg . ml-1) or fetal (1.8 +/- 0.2 pg . ml-1) plasma. After exposure of the ewe to 10% O2 or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P less than 0.001) to 200 +/- 59 pg . ml-1 with a delayed increase in amniotic fluid concentrations (P less than 0.03) to 15.8 +/- 4.5 pg . ml-1. This rise in concentration of vasopressin in amniotic fluid was sustained for at least 24 h and levels at that time were highly correlated with peak plasma concentrations (r = 0.83, P less than 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P less than 0.02) and sustained increase of vasopressin in amniotic fluid. After intraamniotic injection of vasopressin, levels remained increased for at least 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arginine vasopressin response to an osmotic stimulus in the fetal sheep

Baseline plasma osmolality (pOsm) and plasma arginine vasopressin (pAVP) were measured in chronically catheterized fetal sheep. Mean baseline pAVP in fetuses from 101-120 days was 1.9 +/- 0.46 muU/ml (mean +/- SEM) with a pOsm of 293 +/- 1.8 mOsm/kg. In fetuses of 121-141 days of gestation, mean pAVP was significantly lower, 0.77 +/- 0.19 muU/ml (P less than 0.05), with a similar pOsm (293 +/- 1.9 mOsm/kg). The logarithmic baseline pAVP values were linearly correlated with pOsm for both groups. Hypertonic saline infusion resulted in a similar increase in the log pAVP corrected for the rise in pOsm in the 101-120-day fetuses and in 121-141-day fetuses. The slope of this response was similar to that of the steady state relationship. The data indicates that the fetal osmoreceptor system for control of arginine vasopressin secretion is fully functional in the last trimester of pregnancy.     

Vasopressin and catecholamine secretion during metabolic acidemia in the ovine fetus

It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AVP) during intrauterine hypoxia/asphyxia reflects decreases in PaO2 and/or pHa; however, the components of these "stresses," i.e. PO2, PCO2, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PCO2. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 +/- 4 (mean +/- SD) days gestation with 1 M NH4Cl, while monitoring mean arterial pressure, heart rate, PaO2, PaCO2, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, PaO2, PaCO2, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 +/- 0.01 to 7.04 +/- 0.05 (p less than 0.05) during NH4Cl and did not return to control levels until 24 h later. AVP increased from 2.85 +/- 0.23 to 5.26 +/- 1.11 microU/ml (p less than 0.05) at the time of maximum acidosis, correlating with the fall in pHa (r = -0.67, (p = 0.001); however, after stopping NH4Cl, AVP returned to baseline levels although pHa remained less than 7.15. In control studies using the same osmolar load, volume, and rate of infusion, AVP levels were unchanged. Only epinephrine was significantly (p less than 0.05) elevated during acidosis, but did not correlate with pHa or plasma AVP. Marked metabolic acidemia appears to have little or no effect on fetal AVP secretion, and fetal catecholamine secretion is variable.     

Arginine vasopressin during gestation and parturition in sheep fetus.

The possible correlation between plasma arginine vasopressin (AVP) concentration and the processes leading to parturition was assessed in 11 chronically catheterized pregnant ewes. Samples of blood withdrawn intermittently during a 20-day period preceding labor and during parturition were analyzed for AVP by a specific radioimmunoassay, as well as for pH, PaCO2 and PaO2. Fetal AVP was 1.74 +/- 1.55 pg/ml and maternal AVP 1.47 +/- 0.74 pg/ml (mean +/- SD). No preparturient rise in fetal vasopressin was noted, but levels increased progressively during labor to reach peak levels in cord blood (range 7.5--8,000 pg/ml). There was no consistent rise in maternal vasopressin during the same interval. A relationship between prolonged antepartum intrauterine asphyxia and increases in fetal vasopressin was noted. It is concluded that the markedly elevated levels of vasopressin observed in cord blood are the result of intrapartum 'stress', but are not related to the initiation of parturition.     

Control of water balance in infants with bronchopulmonary dysplasia: role of endogenous vasopressin

Babies with chronic bronchopulmonary dysplasia (BPD) can sometimes develop pallor, systemic and pulmonary edema, oliguria, and hyponatremia not attributable to cardiopulmonary or renal impairment. These signs and symptoms might, however, be explained by inappropriate control of vasopressin secretion. To test this hypothesis, we measured plasma vasopressin and osmolality, serum sodium and potassium concentrations, urine output and osmolality, and free water clearance in 26 normoxic infants with BPD aged 1-4 months. All of these infants required supplemental oxygen (FiO2 0.41 +/- 0.03, mean +/- 1 SE) to maintain O2 saturation of greater than 88%, and six infants also required mechanical ventilation. As controls, 10 infants of similar age but without BPD were also studied. None of the infants had been discharged from the nursery and was receiving any medications, and all were clinically stable when studied. Compared to control infants, infants with BPD had significantly elevated plasma vasopressin concentrations (control 5.2 +/- 0.9 pg/ml; BPD 42.4 +/- 5.1; mean +/- SE, p less than 0.05). Moreover, infants with BPD had hyponatremia and hypotonic plasma, and both urine output and free water clearance were significantly reduced. These data suggest that some infants with chronic BPD have elevated vasopressin levels that are functionally significant. We speculate that excessive stimulation of vasopressin secretion may explain some of the pulmonary and nonpulmonary signs and symptoms in infants with chronic BPD.     

Post-hepatic insulin secretion in the fetal lamb

Post-hepatic insulin secretion was measured in six chronically catheterized fetal lambs (fetal weight 2.8 +/- 0.3 kg, mean +/- S.E.M.) and the results were compared with those obtained in nine prematurely delivered newborn lambs (birth weight 3.1 +/- 0.3 kg and postnatal age 1.3 +/- 0.2 days). The fetal and neonatal lambs received either a 0.45% saline or a glucose infusion respectively, which resulted in a 2-fold increase in the plasma glucose concentration. [131I]insulin was infused for 110 min to determine the rate of insulin secretion during a steady state of plasma glucose concentration. Post-hepatic insulin secretion and the metabolic clearance rate were calculated. With the 2-fold rise in plasma glucose concentration, the post-hepatic insulin secretion rate increased significantly in the newborn lamb and in three out of four fetuses. The plasma insulin concentration increased significantly in the fetus (11 +/- 4.0 to 35 +/- 8 microU/ml, P less than 0.05) during glucose stimulation as a result of decreased metabolic clearance rate of insulin (10.6 +/- 1.9 to 6.3 +/- 1.8 ml . kg-1 . min-1) and an increase in post-hepatic insulin secretion rate. In spite of an increase in post-hepatic insulin secretion rate, the increase in plasma insulin concentration in the newborn lamb was not significant because of large variation in the values obtained. The data suggest that pancreatic beta-cells in the newborn and in the fetal lamb are equally responsive to a 2-fold increase in plasma glucose concentration.     

Late hyponatremia in premature infants: role of aldosterone and arginine vasopressin

To assess the possible involvement of arginine vasopressin in the pathogenesis of late hyponatremia in preterm infants, serial measurements of sodium balance, fractional sodium excretion, plasma and urine osmolality and sodium concentration, and urinary aldosterone and arginine vasopressin excretion were performed at weekly intervals in nine healthy preterm infants. During the course of late hyponatremia, there was a significant increase in urinary aldosterone and arginine vasopressin excretion, from 0.94 +/- 0.16 to 4.30 +/- 0.76 micrograms/day and from 0.38 +/- 0.08 to 1.19 +/- 0.26 ng/day, respectively, from the first to the fourth to fifth weeks. A significant negative correlation was found between fractional sodium excretion and urinary aldosterone excretion. Aldosterone excretion, however, correlated positively with urinary arginine vasopressin excretion in seven of the nine infants. The parallel increase in urinary aldosterone and arginine vasopressin excretion in salt-losing premature infants may occur in response to the protracted contraction of the extracellular fluid compartment, and may contribute to the restoration of volume in the body fluid compartments and to the development of late hyponatremia.     

Effects of acute hypercapnia on maternal and fetal vasopressin and catecholamine release

Although fetal asphyxia, i.e. hypoxemia, acidosis, and hypercapnia, increases plasma arginine vasopressin (AVP) greater than 40-fold, hypoxemia and metabolic acidosis occurring independently cause only 5-fold and 2-fold increases, respectively. To determine the effects of hypercapnia on AVP release, we examined the effects of acute hypercapnia on AVP secretion in six pregnant sheep and their fetuses at 135 +/- 4 d (chi +/- SD), exposing the ewe successively to room air, 30% O2, 30% O2 plus 10% CO2, 30% O2, and room air, and monitoring uterine blood flow, as well as maternal and fetal mean arterial pressure, heart rate, arterial blood gases, and plasma AVP and catecholamines. Oxygen exposure had no effect on the ewe or fetus. During O2 plus CO2 exposure, the ewes and fetuses developed hypercapnia in the absence of hypoxia, arterial CO2 tension increasing to 8.38 +/- 0.87 kPa (62.9 +/- 6.5 mm Hg) and 10.0 +/- 0.61 kPa (75.2 +/- 4.6 mm Hg) (p less than 0.001), respectively, at 30 min of exposure. Although fetal heart rate and mean arterial pressure were unchanged, maternal values rose 61 and 30% (p less than 0.001), respectively. At 30 min of O2 + CO2 exposure, maternal norepinephrine increased from 2.23 +/- 0.74 to 8.52 +/- 3.97 nmol/L (p = 0.15) and fetal epinephrine increased from 0.27 +/- 0.10 to 2.271 +/- 0.90 nmol/L (p = 0.01); plasma AVP was not significantly increased in the ewe or fetus, although levels rose from approximately 45 to 127 +/- 48 and 137 +/- 64 pmol/L (p = 0.10), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma arginine vasopressin during transition from fetus to newborn following minimal trauma delivery of lambs and goats

Vasopressin in umbilical arterial and venous blood is high at delivery and may be important in the maintenance of arterial pressure and absorption of lung liquid. We used chronically instrumented near-term fetal lambs and goats to investigate the changes in plasma vasopressin that occur during perinatal cardiovascular transition following cesarean section without labor. Plasma arginine vasopressin was more than 5 times greater 15 min following birth than immediately prior to clamping the umbilicus, and it fell progressively over the ensuing 2-5 h to levels not significantly different from before birth. Fifteen min after delivery, neither arterial pressure, blood gases, nor pH appeared to account for the increase.     

Plasma and cerebrospinal fluid arginine vasopressin in patients with and without fever.

Hyponatraemia has been described in association with a number of acute infectious diseases, mainly bacterial and tuberculous meningitis and pneumonia, and has been attributed to inappropriate secretion of arginine vasopressin (AVP). The mechanism of inappropriate AVP production is uncertain, but there is experimental evidence to suggest that fever may stimulate secretion of AVP into plasma and cerebrospinal fluid. In this study, AVP concentrations in plasma and cerebrospinal fluid from 37 febrile children with infections have been compared with those from 27 afebrile control subjects. Ten of the febrile children had meningitis (eight bacterial, two viral) and the remainder a variety of other infectious diseases. Seventy four per cent of febrile infected children were hyponatraemic (serum sodium less than 135 mmol/l) compared with only 8% of the afebrile controls. Plasma AVP concentrations were significantly higher in the febrile patients (median 2.92 pmol/l, range 1.0-23.25, n = 28) than in controls (median 1.67 pmol/l, range 0.57-6.0, n = 14) but there was no significant difference in cerebrospinal fluid AVP concentrations. There was no difference in plasma AVP concentrations between patients with meningitis and those with infections not involving the central nervous system. Careful attention should be paid to fluid and electrolyte balance in all children with acute infections.     

Ontogeny of gastric function in the pig: acid secretion and the synthesis and secretion of gastrin.

Gastric acid secretion, gastrin-releasing peptide (GRP)-stimulated gastrin secretion and concentrations of somatostatin in gastric tissues were studied in sucking pigs (n = 48). In addition, gastrin concentrations in plasma and antral tissue were measured in fetal and sucking pigs (n = 66) from 22 days before birth (93 days gestation) to 36 days of age. From 3 days of age littermate pairs were treated twice a day with either saline (n = 20) or adrenocorticotropin [ACTH (1-24); n = 20]. Pentagastrin-stimulated acid secretion per unit stomach weight was 39 +/- 7 mumol H+/g/h at 0-1 day, increased to 194 +/- 15 mumol H+/g/h at 5-7 days and plateaued. Antral gastrin concentration was 0.14 nmol/g 10 days before birth and increased to 2.7 nmol/g at 5 weeks of age. Plasma gastrin was 25 +/- 2 pmol/l at 22 days before birth, increased to 102 +/- 14 pmol/l at birth and decreased during the postnatal period. Somatostatin concentrations were higher in antral than fundic tissues (p < 0.05) and remained constant during the postnatal period. Increased levels of glucocorticoids in plasma following ACTH treatment had no effect on the studied parameters except that it reduced basal (p < 0.07) and GRP-stimulated (p < 0.05) plasma gastrin concentrations at 6-7 days of age. Development of acid secretion and its gastric regulatory peptides in the pig is different from that in the rat in that it occurs at an earlier age and does not appear to be greatly influenced by elevated glucocorticoid levels from 3 days after birth.     

Hydration and meningitis]

For almost 20 years, fluid restriction has been applied in the management of bacterial meningitis. This recommendation was based upon the findings of elevated plasma levels of arginine vasopressin in children with bacterial meningitis and their interpretation as evidence for inappropriate secretion of antidiuretic hormone. Recent data indicate that this interpretation was erroneous and that elevated levels of arginine vasopressin is the consequence of hypovolemia in the majority of cases of bacterial meningitis. In addition, fluid restriction appears to worsen the prognosis. As a consequence, not only fluid restriction must not be systematically applied in the management of bacterial meningitis, but appropriate fluid and sodium intakes are necessary to compensate hypovolemia and dehydration. Only a small number of cases with evidence of inappropriate secretion of antidiuretic hormone will require fluid restriction.     

Fetal arginine vasopressin under basal and hypoosmolal conditions

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

Autonomic adjustments to severe hypotension in fetal and neonatal sheep

In fetal sheep, severe hypotension causes heart rate (HR) slowing. Studies during development have also shown that a reflex bradycardia and hypotension can be elicited after chemostimulation with veratridine and is dependent on the age of the animal. In adults, a vagally mediated depressor reflex characterized by bradycardia, hypotension, and withdrawal of efferent sympathetic activity can be observed after stimulation of chemosensitive or mechanosensitive cardiac receptors with veratridine or in circumstances of reduced cardiac filling. This reflex, known as the Bezold-Jarisch reflex, plays a role in disease states such as myocardial ischemia and hemorrhage. The objectives of our study were to determine whether a sympathoinhibitor depressor reflex, along with the bradycardia, is observed during pharmacologically induced hypotension in fetal and newborn lambs. In both fetal and newborn lambs, HR and renal sympathetic nerve activity (RSNA) initially increased (p < 0.05) in response to nitroprusside infusion to reach a maximum value. The range (or "plateau") of mean arterial blood pressure over which maximum RSNA was maintained constant before withdrawal of sympathetic tone started to be observed was significantly (p < 0.05) smaller in fetuses (0.3 +/- 0.3 mm Hg) than newborn (6 +/- 1 mm Hg) lambs. Similarly, the plateau over which maximum HR was maintained before onset of bradycardia was significantly smaller in fetuses (4 +/- 1 versus 11 +/- 2 mm Hg). The mean arterial blood pressure level ("threshold") at which a depressor reflex was triggered was significantly (p < 0.05) lower in fetal than newborn sheep (35 +/- 2 versus 53 +/- 3 mm Hg for HR and 35 +/- 2 versus 57 +/- 2 mm Hg for RSNA). The rates of fall (slopes) for both HR and RSNA were also significantly (p < 0.05) more pronounced in fetuses (1.85 +/- 0.27 and 6.08 +/- 2.45%/mm Hg) than in newborns (1.21 +/- 0.16 and 1.97 +/- 0.32%/mm Hg). Bilateral vagotomy significantly increased the plateau of mean arterial blood pressure over which maximum RSNA and HR were maintained constant. Vagotomy also decreased the threshold for both RSNA and HR and the slope of the RSNA response to the nitroprusside infusion in newborn lambs. Results from this study show that activation of the arterial baroreflex during nitroprusside-induced hypotension is followed by withdrawal of sympathetic tone and bradycardia and that this depressor reflex is more pronounced in late-gestation fetuses than newborn lambs and is significantly attenuated after bilateral vagotomy in newborn lambs.