Placental norepinephrine clearance: in vivo measurement and physiological role

1995 ◽  
Vol 269 (1) ◽  
pp. E145-E149 ◽  
Author(s):  
L. Bzoskie ◽  
L. Blount ◽  
K. Kashiwai ◽  
Y. T. Tseng ◽  
W. W. Hay ◽  
...  
Keyword(s):  
Production Rate ◽  
Umbilical Vein ◽  
Physiological Role ◽  
Total Clearance ◽  
Clearance Rates ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
In Vivo Measurement ◽  
A Site

The intrauterine clearance rate of catecholamines is higher than in newborn animals or in adults. The separate contributions of the fetus and placenta to this clearance are not known. The placenta is a site of expression of the amine plasma membrane transporters that mediate this process. To determine the physiological role of this placental transporter in vivo, we studied fetal sheep at 123 days with common umbilical vein (UV), fetal arterial (AO), and venous catheters. Tritiated norepinephrine ([3H]NE) was infused to determine the kinetics of placental and fetal NE appearance and clearance rates. Umbilical flow was determined by [3H]NE infusion. Placental and total (fetal-placental) NE clearance rates were determined by measurement of [3H]NE from simultaneously drawn UV and AO samples. Total clearance was 99 +/- 8 ml.kg-1.min-1. Placental fractional [3H]NE extraction was 21% and accounted for 48% of total clearance. Fetal plasma NE production rate was 85 +/- 20 ng.kg-1.min-1. We conclude that placental catecholamine clearance is an important metabolic function of the placenta. This mechanism for clearance of the high fetal production rate of catecholamines is vital for fetal homeostasis. We speculate that derangements in placental catecholamine clearance may explain the exaggerated adverse effects on the fetus of drugs like cocaine, which block catecholamine transport.

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep

2000 ◽  
Vol 279 (3) ◽  
pp. H1166-H1171 ◽  
Author(s):  
Torvid Kiserud ◽  
Takashi Ozaki ◽  
Hidenori Nishina ◽  
Charles Rodeck ◽  
Mark A. Hanson
Keyword(s):  
Nitric Oxide ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Umbilical Vein ◽  
Ductus Venosus ◽  
Adrenergic Agonist ◽  
Fetal Sheep ◽  
Vasoactive Substances ◽  
Ultrasound Measurements

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial Po2(Pao2) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 μg · kg−1· min−1) or the α1-adrenergic agonist phenylephrine (6.5 μg · kg−1· min−1) into the umbilical vein or during hypoxemia (fetal PaO2reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an α1-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV.

Alterations in oxytocin prohormone processing during early development in the fetal sheep

1992 ◽  
Vol 263 (3) ◽  
pp. R738-R740 ◽  
Author(s):  
M. Morris ◽  
M. Castro ◽  
J. C. Rose
Keyword(s):  
Fetal Development ◽  
Plasma Levels ◽  
Umbilical Artery ◽  
Umbilical Vein ◽  
Late Gestation ◽  
Developmental Changes ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Prohormone Processing ◽  
Specific Antisera

Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma.

scholarly journals Inhibition of Brain Prostaglandin Endoperoxide Synthase-2 Prevents the Preparturient Increase in Fetal Adrenocorticotropin Secretion in the Sheep Fetus

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4128-4136 ◽  
Author(s):  
Jason Gersting ◽  
Christine E. Schaub ◽  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fetal Brain ◽  
Brain Regions ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Prostaglandin Endoperoxide ◽  
Fetal Plasma ◽  
Prostaglandin Endoperoxide Synthase

Maturation of the fetal hypothalamus-pituitary-adrenal axis is critical for the timely somatic development of the fetus and readiness for birth. Recently, we proposed that prostaglandin generation within the fetal central nervous system is critical for the modulation of hypotension-induced fetal ACTH secretion. The present study was designed to test the hypothesis that the preparturient increase in fetal ACTH secretion is dependent upon fetal central nervous system prostaglandin synthesis mediated by the activity of prostaglandin endoperoxide synthase (PGHS)-2 (cyclooxygenase-2) in the fetal brain. We performed two studies in chronically catheterized fetal sheep. In the first study, we infused nimesulide or vehicle intracerebroventricularly (icv) into singleton fetal sheep and collected blood samples until spontaneous parturition. Nimesulide significantly delayed parturition, and inhibited fetal ACTH and proopiomelanocortin secretion but did not prevent the preparturient increase in fetal plasma cortisol concentration. In the second study, we used twin fetuses. One fetus received intracerebroventricular nimesulide and the other intracerebroventricular vehicle. Nimesulide reduced brain tissue concentrations of prostaglandin estradiol, while not affecting plasma prostaglandin E2 concentrations, demonstrating an action restricted to the fetal brain. Nimesulide reduced PGHS-2 mRNA and increased PGHS-2 protein, while not altering PGHS-1 mRNA or protein in most brain regions, suggesting an effect of the inhibitor on PGHS-2 turnover and relative specificity for PGHS-2 in vivo. We conclude that the preparturient increase in fetal ACTH and proopiomelanocortin is dependent upon the activity of PGHS-2 in the fetal brain. However, we also conclude that the timing of parturition is not solely dependent upon ACTH in this species.

High-density lipoproteins (HDL) stimulate placental lactogen secretion in pregnant ewes: further evidence for a role of HDL in placental lactogen secretion during pregnancy

1989 ◽  
Vol 120 (3) ◽  
pp. 423-427 ◽  
Author(s):  
A. Grandis ◽  
V. Jorgensen ◽  
L. Kodack ◽  
S. Quarfordt ◽  
S. Handwerger
Keyword(s):  
Physiological Role ◽  
Maternal Plasma ◽  
High Density ◽  
Placental Lactogen ◽  
High Density Lipoproteins ◽  
Indwelling Catheter ◽  
Fetal Plasma ◽  
Sds Page

ABSTRACT Previous studies from our laboratory showed that high-density lipoproteins (HDL) stimulate the release of human placental lactogen (PL) from cultured trophoblast cells from normal pregnant women. To determine whether HDL stimulates PL secretion in vivo, ovine HDL was infused over 2–5 min into 11 pregnant ewes (22 separate experiments) at 86–130 days of gestation via an indwelling catheter into the maternal jugular vein. The HDL, freshly prepared from the plasma of pregnant ewes by differential flotation ultracentrifugation, was greater than 99% purified as judged by SDS-PAGE. Plasma samples were obtained from the ewes before and at 0·5-h intervals for 6 h following the infusions and were assayed for PL by a specific homologous radioimmunoassay. The maternal infusion of HDL at doses of 302–784 mg (5·3–13·8 mg/kg body weight) stimulated significant increases in maternal plasma PL concentrations in six out of eight experiments (six ewes), and the infusion of 108–264 mg (1·9–4·6 mg/kg) stimulated plasma PL concentrations in two out of six experiments. In contrast, HDL at doses < 100 mg were without effect in eight experiments. The response to the HDL infusions was characterized by a sustained increase in plasma PL concentrations beginning 1·5–2·5 h after the infusions, reaching a maximum 274·2 ± 21·9% of the baseline value (P<0·001). In contrast, the maternal infusion of lipoprotein-free plasma proteins or saline had no effect on maternal plasma PL concentrations. Although the infusion of HDL into pregnant ewes stimulated an increase in maternal plasma PL concentrations, the infusion of HDL (0·8–22·0 mg/kg) into three fetuses in seven separate experiments had no effect on fetal plasma PL concentrations. The demonstration that HDL stimulates an increase in plasma PL concentrations in pregnant ewes strongly supports a novel physiological role for HDL in the regulation of PL secretion. Journal of Endocrinology (1989) 120, 423–427

scholarly journals In Vivo Evidence for Stimulation of Placental, Myometrial, and Endometrial Prostaglandin G/H Synthase 2 by Fetal Cortisol Replacement after Fetal Adrenalectomy

Endocrinology ◽  
2001 ◽  
Vol 142 (9) ◽  
pp. 3857-3864 ◽  
Author(s):  
W. X. Wu ◽  
X. H. Ma ◽  
N. Unno ◽  
P. W. Nathanielsz
Keyword(s):  
Plasma Cortisol ◽  
Treated Group ◽  
Late Gestation ◽  
Premature Labor ◽  
Indirect Pathway ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Estrogen Synthesis ◽  
Stimulation Of

Abstract Fetal glucocorticoid-induced premature labor in sheep is an established model of premature labor. However, the pathways by which fetal cortisol triggers subsequent maternal endocrine changes, including enhanced PG synthesis, leading to labor are unclear. The current study was undertaken to determine whether cortisol administration to adrenalectomized fetuses to clamp fetal cortisol at levels present early in the late gestation rise, which are inadequate to produce labor, can stimulate placental, myometrial, and endometrial prostaglandin G/H synthase 2 mRNA and protein expression. At 109–113 d gestation, fetal sheep adrenals were removed (n = 8), or sham surgery was performed (n = 4). From d 6 postadrenalectomy, maternal and fetal plasma cortisol were determined daily by RIA. From d 7 postadrenalectomy, cortisol (4 μg/min) was continuously infused iv to four adrenalectomized fetuses. Endometrium, myometrium, and placentome were collected from all three groups of ewes (n = 4 for each group), and total RNA and proteins were extracted from each intrauterine tissue and analyzed by Northern and Western for prostaglandin G/H synthase 2 mRNA and protein. P45017α hydroxylase mRNA was analyzed in the placentome by Northern blot. Data were analyzed by ANOVA. Plasma cortisol levels remained low in sham-operated and adrenalectomized fetus, whereas during cortisol infusion to adrenalectomized and cortisol-treated fetuses, plasma cortisol increased to the late gestation level. After adrenalectomy, prostaglandin G/H synthase 2 did not change in any tissue studied. Fetal plasma cortisol replacement to late gestation levels increased prostaglandin G/H synthase 2 to levels similar to term levels in all three tissues. PGHS1 mRNA and protein did not change in any group studied. There was a minimal increase in P45017α hydroxylase mRNA in the placentome in the adrenalectomized and cortisol-treated group. Cortisol- induced labor further increased P45017α hydroxylase mRNA in the placentome compared with that in adrenalectomized and cortisol-treated animals. These data provide evidence for in vivo cortisol up-regulation of prostaglandin G/H synthase 2, but not PGHS1, in late gestation in the ovine placentome, myometrium, and endometrium. As stimulation of the estrogen biosynthetic pathway was minimal in the adrenalectomized and cortisol-treated group, these data provide support for the concept that cortisol has a direct effect on prostaglandin G/H synthase 2 expression in addition to its classical indirect pathway on prostaglandin G/H synthase 2 as a result of estrogen synthesis.

Plasma epinephrine appearance and clearance rates in fetal and newborn sheep

1993 ◽  
Vol 265 (4) ◽  
pp. R756-R760 ◽  
Author(s):  
H. Stein ◽  
K. Oyama ◽  
A. Martinez ◽  
B. Chappell ◽  
J. Padbury
Keyword(s):  
Clearance Rate ◽  
Whole Body ◽  
Plasma Catecholamine ◽  
Fetal Life ◽  
Plasma Epinephrine ◽  
Clearance Rates ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Appearance Rate ◽  
Catecholamine Levels

Newborn plasma catecholamine levels are elevated compared to fetal life. Whether this reflects increased catecholamine secretion after birth or decreased clearance is not known. To determine the plasma appearance and clearance rates for catecholamines during the transition to postnatal life, we compared plasma epinephrine appearance and clearance rates in fetal sheep before birth and in newborns after delivery. Plasma epinephrine appearance and clearance rates were measured by radiotracer analysis in eight fetuses at 127 +/- 1 days of gestation and, after cesarean delivery, at 130 +/- 1 days of gestation. There was no difference in plasma epinephrine appearance rate during the fetal (26 +/- 4 ng.kg-1 x min-1) or newborn studies (31 +/- 5 ng.kg-1 x min-1). The fetal plasma epinephrine clearance rate (131 +/- 13 ml.kg-1 x min-1) was significantly higher than newborn plasma epinephrine clearance rate (40 +/- 3 ml.kg-1 x min-1). Thus fetal plasma epinephrine appearance rate is not different from appearance rate in the immediate newborn period when catecholamine levels are higher than during most other physiological circumstances. The increase in circulating catecholamine levels at birth is due in part to a significant decrease in clearance rate. It is likely that removal of the placental contribution to whole body clearance accounts for much of the difference observed in fetal and newborn clearance rates.

scholarly journals Enteral IGF-I enhances fetal growth and gastrointestinal development in oesophageal ligated fetal sheep

1999 ◽  
Vol 162 (2) ◽  
pp. 227-235 ◽  
Author(s):  
RM Kimble ◽  
BH Breier ◽  
PD Gluckman ◽  
JE Harding
Keyword(s):  
Amniotic Fluid ◽  
Fetal Growth ◽  
Physiological Role ◽  
Treated Group ◽  
Spleen Weight ◽  
Gut Development ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Gut Function ◽  
Igf I

Infants with upper gut atresia often have impaired intrauterine growth and gut function. IGF-I is important in fetal growth and is contained in amniotic fluid. We therefore wanted to test the hypothesis that IGF-I infused into fetal gut would reverse the effects of an upper gut obstruction on gut structure and growth in fetal sheep. At 90 days gestation fetuses (n=6 per group) underwent oesophageal ligation, followed by continuous infusion of IGF-I (1-8 microgram/day) or saline into the gut beyond the ligation until 137 days. Controls underwent sham ligation only. Oesophageal ligation tended to reduce fetal body and organ weights. IGF-I treatment prevented this reduction and increased body length and spleen weight above those of controls. The decrease in bowel wall thickness induced by oesophageal ligation was also prevented by IGF-I treatment. Amniotic fluid IGF-I concentrations did not change over gestation and were higher in the IGF-I treated group. No change in fetal plasma IGF-I concentrations were detectable. We conclude that enterally administered IGF-I may enhance fetal growth and gut development in utero and that IGF-I in amniotic fluid may play a physiological role in gut development in the fetus.

scholarly journals Biological Activity of 17β-Estradiol-3-Sulfate in Ovine Fetal Plasma and Uptake in Fetal Brain

Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 599-604 ◽  
Author(s):  
Charles E. Wood ◽  
Kelly E. Gridley ◽  
Maureen Keller-Wood
Keyword(s):  
Hpa Axis ◽  
Active Form ◽  
Fetal Brain ◽  
Late Gestation ◽  
Biologically Active ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hpa Axis Activity

In sheep, the fetal hypothalamus-pituitary-adrenal axis plays a central role in the initiation of parturition. We have reported that estradiol dramatically increases the activity of the fetal hypothalamus-pituitary-adrenal (HPA) axis. Sulfoconjugated estrogens are known to circulate in high concentrations in fetal plasma. We have reported the expression and abundant activity of steroid sulfatase within the fetal brain regions important for HPA axis control, and we have proposed that sulfoconjugated estrogens in fetal plasma are deconjugated (and therefore converted to a biologically active form) in fetal brain. The present study was designed to test the hypothesis that exogenous estradiol-3-sulfate stimulates HPA axis activity in late gestation fetal sheep and that it is concentrated by fetal brain tissue. We infused estradiol-3-sulfate iv into fetal sheep (125–135 d gestation; term = 147 d) at rates of 0, 0.25, and 1.0 mg/d for 5 d and performed serial sampling of fetal blood before and at the end of the infusion periods. Infusions increased fetal plasma estradiol-3-sulfate concentrations and produced dose-related increases in HPA axis activity. The action of the steroid on the fetal brain was also demonstrated as dose-related increases in the abundance of Fos in fetal cerebellum. In a second study we measured the uptake of sulfoconjugated and unconjugated estrogen (estrone-3sulfate and estrone, respectively) into the fetal brain (124–128 d gestation) in vivo. Both forms of estrogen were concentrated in fetal brain, with the uptake of estrone greater than that of estrone-3-sulfate. We conclude that sulfoconjugated estrogens augment fetal HPA axis activity and that they can cross the fetal blood-brain barrier. We propose that in late gestation the large circulating pool of sulfoconjugated estrogen is a biologically important source of active hormone that might play a role in the timing of parturition in sheep.

Osmotic flow through the placental barrier of chronically prepared sheep

1977 ◽  
Vol 233 (4) ◽  
pp. H466-H474 ◽  
Author(s):  
T. Armentrout ◽  
S. Katz ◽  
K. L. Thornburg ◽  
J. J. Faber
Keyword(s):  
Freezing Point ◽  
Umbilical Vein ◽  
Water Flux ◽  
Maternal Plasma ◽  
Vapor Pressure Osmometry ◽  
Blood Flows ◽  
Fetal Plasma ◽  
Diffusional Permeability ◽  
Pregnant Ewe

An electromagnetic flow sensor was placed on the distal aorta of sheep fetuses in utero, and catheters were placed in a femoral artery and the common umbilical vein. Catheters were also placed in a carotid artery and a uterine vein of the pregnant ewe. Three days postoperatively maternal plasma was hyperosmotic with respect to fetal plasma by all methods: +5.8 +/- 1.4 SE by vapor-pressure osmometry, +2.2 +/- 0.7 SE by freezing-point depression osmometry corrected for bicarbonate loss; and +3.26 mosmol/liter by chemical measurement of plasma constituents. Maternal or fetal plasma was made hypertonic in vivo by infusion of concentrated solutions of mannitol, sucrose, or NaCl. Transplacental water flux was calculated from placental blood flows and arteriovenous differences in water content of the blood. The apparent osmotic conductivity of the placenta was 61 ml2-mosmol-1-kg-1, but this value should be divided by an unknown reflection coefficient to yield the true osmotic conductivity. Separate measurements were made of the placental diffusional permeability of Na+ and Cl- in five chronically prepared sheep fetuses: PSNa+ =0.20 +/- 0.04, PSCl- = 0.27 +/- 0.04 ml/(min-kg fetus). There was a highly significant positive regression between (total) placental permeability and fetal weight.

METABOLIC CLEARANCE RATE, PRODUCTION RATE AND MAMMARY UPTAKE OF PROGESTERONE IN THE GOAT

1975 ◽  
Vol 64 (3) ◽  
pp. 485-502 ◽  
Author(s):  
R. B. HEAP ◽  
C. A. BEDFORD ◽  
J. L. LINZELL
Keyword(s):  
Mammary Gland ◽  
Production Rate ◽  
Clearance Rate ◽  
Venous Blood ◽  
Physiological Role ◽  
Mammary Tissue ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Normal Cycle

SUMMARY The dynamics of progesterone uptake and metabolism in the mammary gland of the goat have been measured and related to the metabolic clearance rate and production rate of the hormone determined by tracer kinetic techniques. The metabolic clearance rate of progesterone from blood was 3·13 ± 0·35 (s.e.m.) 1/min in ten experiments on six goats; values tended to be slightly higher in pregnant than in non-pregnant goats. The production rate of progesterone at oestrus, and at day 3 of the normal cycle, was less than 0·01 μg/min. During the luteal phase of the oestrous cycle the production rate was 8·5 and 14·6 μg/min in 2 animals, and in the second half of pregnancy, 15·3 ± 0·6 μg/min (5 animals). Progesterone was extracted from the circulation by the mammary gland of conscious goats with an efficiency of 49·4 ± 11·3% in non-pregnant, and 51·7 ± 11·5% in pregnant animals. The mean clearance rate of progesterone by the udder was 0·2791/min, 8·8% of the metabolic clearance rate. Mammary uptake of progesterone in goats with an actively secreting corpus luteum was 0·64 ± 0·29μg/min, which gave an estimated value of 0·11– 1·88 ng/min/g mammary gland. The mammary extraction of progesterone was investigated in a goat 3 days after oestrus when any high affinity receptor sites would presumably be unoccupied. During the infusion of progesterone into a mammary artery, tissue samples were taken from various organs, including the mammary gland, and the concentration of labelled compounds at steady state was determined. A high mammary extraction of progesterone was found to be attributable principally to progesterone metabolism. The metabolites of progesterone were removed from the gland in venous blood and were not stored to any appreciable extent in mammary tissue. Experiments in vitro confirmed the findings in vivo that mammary tissue metabolized labelled progesterone and also pregnenolone and androstenedione; metabolism of dehydroepiandrosterone, oestradiol-17β, oestrone and cortisol was relatively small. Confirmation of our previous finding that the mammary gland of the goat can synthesize progesterone from labelled pregnenolone infused into the gland in vivo, further implicates this organ as an active site of metabolism of certain steroids. The physiological role of steroid metabolism in the mammary gland is discussed.

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