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Arginine vasopressin (AVP) is a peptide hormone which is found in neurons within the paraventricular (PVN) and the supraoptic (SON) nuclei of the hypothalamus. In fetal sheep, this neuropeptide is involved in maturational processes and adaptive responses to 'stress'. This study examined the effect of age on the total number and distribution of AVP-containing neurons in the PVN and SON of fetal sheep and newborn lambs by quantitative light-microscopic immunocytochemistry. Serial coronal sections of hypothalami from three groups of animals were studied: fetuses at 104-109 days of gestation (n = 6) comprising the early group, fetuses at 130-139 days of gestation (n = 5) comprising the late group and newborn lambs at 12-20 postnatal days (n = 5) comprising the neonatal group. This period of development was chosen since adaptive mechanisms to stress are operative at or near the time of birth. Hypothalamic dimensions were measured to determine if maturation had an effect on the size of the AVP-containing subregions of the hypothalamus during this period of development. Dimensions included: ventricle height, optic chiasm width, distances from the dorsal margin of the ventricle to the lateral and medial margins of the optic tract, and distance between the medial margins of the optic tracts. As expected, with increase in maturational age, overall dimensions of the AVP-containing subregions increased significantly (p < 0.05). When early- and late-gestation fetuses were compared to newborn lambs, there was a significant increase in the total number of immunoreactive neurons in both the PVN (p < 0.01, Anova) and SON (p < 0.001, Anova) with age. With advancing age, we also observed an increase in the density of AVP neurons in the middle subregion of the PVN and in the midrostral subregion of the SON. These data suggest that, during the late gestational and early postnatal period, de novo synthesis of AVP genes occurs in these hypothalamic nuclei. This study provides a baseline for further investigation to study the effects of stress on these neurons in the developing ovine fetus and newborn lamb.

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)

In the fetus, arginine vasopressin (AVP) has been considered a "stress" hormone with primarily cardiovascular effects. In adult animals, AVP also has substantial endocrine effects, e.g., acting as a corticotropin-releasing factor, an effect not clearly demonstrated in the fetus. Therefore we examined this action of AVP in fetal sheep [135 +/- 1 (SE) days gestation] during a 30-min vasopressin infusion (12 mU/min) while monitoring mean arterial pressure (MAP) and heart rate (HR). Blood samples were obtained before, 15 and 30 min during, and 30 and/or 60 min after the infusion. During vasopressin infusion (n = 11), MAP increased (P less than 0.01), whereas HR fell (P less than 0.01). Plasma AVP increased from 2.32 +/- 0.22 to 84 +/- 6.8 and 89 +/- 10 microU/ml (P less than 0.001), whereas adrenocorticotropin (ACTH) rose from 18.0 +/- 2.4 to 27.7 +/- 3.7 and 43.4 +/- 8.0 pg/ml (P less than 0.05) and cortisol from 1.81 +/- 0.36 to 3.48 +/- 0.56 and 3.97 +/- 0.57 micrograms/dl (P less than 0.005) at 15 and 30 min, respectively. Although neither basal nor AVP-induced ACTH increases changed over the period of gestation studied, base-line cortisol concentrations and the absolute rise in ACTH-stimulated cortisol release increased as gestation progressed, demonstrating increased adrenal sensitivity to ACTH. As in adults, AVP stimulates fetal pituitary secretion of ACTH, providing evidence for another role for AVP in fetal adaptation.

The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (microU/mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n = 13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (greater than 200 microU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of approximately 400 mosmol/kg at urinary AVP levels less than 200 microU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.