Biomedical subjects

Abigail L Fowden

Publications and source records attributed to Abigail L Fowden.

At least 19 recordsLinked to original sources

PubMed2006

Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus.

Clinically, treatment of pregnant women at risk of preterm delivery with synthetic glucocorticoids accelerates fetal maturation. This study investigated the effect of maternal dexamethasone treatment, in clinically relevant doses, on plasma thyroid hormone concentrations and tissue deiodinase activities (D1, D2, and D3) in ewes and their fetuses. From 125 d of gestation (term 145 +/- 2 d), pregnant ewes were injected twice im with either saline (2 ml of 0.9% NaCl, n = 11) or dexamethasone (2 x 12 mg in 2 ml of saline, n = 10) at 24-h intervals. Maternal dexamethasone treatment increased plasma T(3) and reverse T(3) (rT(3)), but not T(4), concentrations in the fetuses. In the dexamethasone-exposed fetuses, hepatic D1 activity was higher, and renal and placental D3 activities were lower, than in the saline-exposed fetuses. In the ewes, plasma concentrations of T(3) and T(4) were reduced, and rT(3) increased, by dexamethasone treatment without any change in tissue deiodinase activity. Therefore, maternal dexamethasone treatment has different effects on the thyroid hormone axis of the pregnant ewe and fetus. In the fetus, the dexamethasone-induced rise in circulating T(3) may be due to both increased hepatic production of T(3) from T(4), and reduced clearance of T(3) by the kidney and placenta. Changes in T(3) bioavailability may mediate some of the maturational effects of antenatal glucocorticoid treatment in the preterm fetus.

Animals↗

PubMed2006

Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term.

Preterm infants have low serum T4 and T3 levels, which may partly explain the immaturity of their tissues. Deiodinase enzymes are important in determining the bioavailability of thyroid hormones: deiodinases D1 and D2 convert T4 to T3, whereas deiodinase D3 inactivates T3 and produces rT3 from T4. In human and ovine fetuses, plasma T3 rises near term in association with the prepartum cortisol surge. This study investigated the developmental effects of cortisol and T3 on tissue deiodinases and plasma thyroid hormones in fetal sheep during late gestation. Plasma cortisol and T3 concentrations in utero were manipulated by exogenous hormone infusion and fetal adrenalectomy. Between 130 and 144 d of gestation (term 145+/-2 d), maturational increments in plasma cortisol and T3, and D1 (hepatic, renal, perirenal adipose tissue) and D3 (cerebral), and decrements in renal and placental D3 activities were abolished by fetal adrenalectomy. Between 125 and 130 d, iv cortisol infusion raised hepatic, renal, and perirenal adipose tissue D1 and reduced renal and placental D3 activities. Infusion with T3 alone increased hepatic D1 and decreased renal D3 activities. Therefore, in the sheep fetus, the prepartum cortisol surge induces tissue-specific changes in deiodinase activity that, by promoting production and suppressing clearance of T3, may be responsible for the rise in plasma T3 concentration near term. Some of the maturational effects of cortisol on deiodinase activity may be mediated by T3.

Animals↗

PubMed2006

Development of the ovine fetal cardiovascular defense to hypoxemia towards full term.

We tested the hypothesis that fetal cardiovascular responses to hypoxemia change close to full term in relation to the prepartum increase in fetal basal cortisol and investigated, in vivo, the neural and endocrine mechanisms underlying these changes. Fetal heart rate and peripheral hemodynamic responses to 1 h of hypoxemia were studied in 25 chronically instrumented sheep within three narrow gestational age ranges: 125-130 (n = 13), 135-140 (n = 6), and >140 (n = 6) days (full term approximately 145 days). Chemoreflex function and plasma concentrations of vasoconstrictor hormones were measured. Reductions in fetal arterial Po(2) during hypoxemia were similar at all ages. At 125-130 days, hypoxemia elicited transient bradycardia, femoral vasoconstriction, and increases in plasma concentrations of catecholamines, neuropeptide Y (NPY), AVP, ACTH, and cortisol. Close to full term, in association with the prepartum increase in fetal basal cortisol, there was a developmental increase in the magnitude and persistence of fetal bradycardia and in the magnitude of the femoral constrictor response to hypoxemia. The mechanisms mediating these changes close to full term included increases in the gain of chemoreflex function and in the magnitudes of the fetal NPY and AVP responses to hypoxemia. Data combined irrespective of gestational age revealed significant correlations between fetal basal cortisol and fetal bradycardia, femoral resistance, chemoreflex function, and plasma AVP concentrations. The data show that the fetal cardiovascular defense to hypoxemia changes in pattern and magnitude just before full term because of alterations in the gain of the neural and endocrine mechanisms mediating them, in parallel with the prepartum increase in fetal basal cortisol.

Acid-Base Equilibrium↗

PubMed2006

Development of baroreflex function and hind limb vascular reactivity in the horse fetus.

This study investigated, in vivo, the mechanisms underlying the development of cardiovascular function in the horse fetus, with particular relevance to baroreflex function and hind limb vascular arterial reactivity to constrictor agonists. Under general anaesthesia, vascular catheters were inserted and a Transonic flow probe was implanted around one of the metatarsal arteries of 13 horse fetuses, either at 0.6 of gestation (n= 6) or at 0.9 of gestation (n= 7, term approximately 335 days). At least 5 days after surgery, pressor, vasoconstrictor and cardiac chronotropic responses to exogenous bolus doses of phenylephrine, angiotensin II and arginine vasopressin were recorded. Fetal cardiac baroreflex slopes were obtained using the peak pressor and heart rate responses to increasing doses of phenylephrine. Fetal treatment with phenylephrine, angiotensin II and vasopressin produced significant changes in arterial blood pressure, hind limb vascular resistance and heart rate. Pressor and vasopressor responses to all agonists were greater at 0.9 than at 0.6 of gestation; however, fetal cardiac baroreflex sensitivity decreased with advancing gestational age. Correlation analysis revealed that fetal plasma cortisol rather than gestational age was a greater determinant of pressor and vasopressor reactivity. In contrast, gestational age rather than cortisol better determined heart rate and baroreflex responsiveness in the equine fetus. The data show that development of cardiovascular function in the equine fetus occurs via cortisol-dependent and -independent pathways.

Animals↗

PubMed2006

Intrauterine programming of physiological systems: causes and consequences.

The intrauterine conditions in which the mammalian fetus develops have an important role in regulating the function of its physiological systems later in life. Changes in the intrauterine availability of nutrients, oxygen, and hormones program tissue development and lead to abnormalities in adult cardiovascular and metabolic function in several species. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes, which can lead to overt disease, particularly with increasing age.

Aging↗

PubMed2005

Development of cardiovascular function in the horse fetus.

In mammals, the mechanisms regulating an increase in fetal arterial blood pressure with advancing gestational age remain unidentified. In all species studied to date, the prepartum increase in fetal plasma cortisol has an important role in the maturation of physiological systems essential for neonatal survival. In the horse, the prepartum elevation in fetal cortisol and arterial blood pressure are delayed relative to other species. Hence, the mechanisms governing the ontogenic increase in arterial blood pressure in the horse fetus may mature much closer to term than in other fetal animals. In the chronically instrumented pony mare and fetus, this study investigated how changes in fetal peripheral vascular resistance, in plasma concentrations of noradrenaline, adrenaline and vasopressin, and in the maternal-to-fetal plasma concentration gradient of oxygen and glucose relate to the ontogenic changes in fetal arterial blood pressure and fetal plasma cortisol concentration as term approaches. The data show that, towards term in the horse fetus, the increase in arterial blood pressure occurs together with reductions in metatarsal vascular resistance, elevations in plasma concentrations of cortisol, vasopressin, adrenaline and noradrenaline, and falls in the fetal : maternal ratio of blood P(a,O(2)) and glucose concentration. Correlation analysis revealed that arterial blood pressure was positively related with plasma concentrations of vasopressin and noradrenaline, but not adrenaline in the fetus, and inversely related to the fetal : maternal ratio of blood P(a,O(2)), but not glucose, concentration. This suggests that increasing vasopressinergic and noradrenergic influences as well as changes in oxygen availability to the fetus and uteroplacental tissues may contribute to the ontogenic increase in fetal arterial blood pressure towards term in the horse.

Animals↗

PubMed2005

Endocrine and metabolic programming during intrauterine development.

In humans, low birth weight is associated with an increased risk of metabolic dysfunction in adult life. Many of these metabolic disorders have an endocrine origin and are accompanied by abnormal hormone concentrations. This has led to the hypothesis that adult metabolic disease arises in utero as a result of programming of key endocrine systems during suboptimal intrauterine conditions associated with fetal growth retardation. This review examines the experimental evidence for prenatal endocrine programming with particular emphasis on endocrine axes involved in growth and metabolism, namely, the hypothalamic-pituitary-adrenal axis, the endocrine pancreas and the somatotrophic axis. It also considers how changes in these endocrine systems contribute to the programming of metabolism in later life.

Endocrine System↗

PubMed2004

Progestagen profiles during the last trimester of gestation in Thoroughbred mares with normal or compromised pregnancies.

Progesterone (P4), pregnenolone (P5) and their metabolites are present in maternal plasma in pregnant mares. It is believed that one of these progestagens may maintain myometrial quiescence. The aims of this study were to identify specific progestagens in pregnant mares' plasma and determine whether these differed between mares with healthy or compromised pregnancies. Jugular blood samples were collected between 243 and 351 days gestation from 19 healthy Thoroughbred mares and 14 mares with placental pathology, including placentitis, and other clinical problems (uterine torsion/rupture, colic, laminitis). Ten progestagens were identified using gas chromatography-mass spectrometry, of which seven increased significantly with gestational age in healthy mares while P4 was undetectable. Mares with placentitis had increased concentrations of either P5 and/or P4 and several metabolites (5alpha-DHP, P5betabeta, betabeta-diol, betaalpha-diol, 20alpha-5P) suggesting increased fetal production of P5 and/or P4 and increased metabolism in the utero-placental tissues in response to chronic stress. Mares with other placental pathology had raised P4 concentrations while 5alpha-DHP and 3beta-5P were low possibly due to reduced placental function. In mares with problems unrelated to the placenta, most progestagens were substantially lower than control values. Although progestagen profiles differed between normal and abnormal pregnancies, no clear link was demonstrated between maternal plasma concentrations of P4, 5alpha-DHP or any other progestagen and the maintenance of pregnancy.

Abortion, Veterinary↗

PubMed2004

Effects of gestational age and cortisol treatment on ovine fetal heart function in a novel biventricular Langendorff preparation.

Structural and functional maturation of a number of fetal organs and physiological systems occurs in the immediate period prior to term, in association with the prepartum increase in fetal plasma cortisol concentration. At present, little is known about how myocardial sensitivity to adrenergic and muscarinic cholinergic stimulation changes as the fetus approaches term, nor the role of the prepartum increase in plasma cortisol concentration in mediating these changes. This study used a novel Langendorff, biventricular, ovine fetal heart preparation to investigate the effects of advancing gestation and cortisol treatment on myocardial sensitivity to adrenergic (isoprenaline) and muscarinic cholinergic (carbachol) stimulation. It was hypothesized that cortisol infusion would fully mimic developmental changes in myocardial responsiveness to adrenergic and cholinergic stimulation. Sixteen Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters. At 125 +/- 1 days gestational age (dGA; term, 145 dGA) fetuses were infused with saline vehicle (n= 7; Premature Control) or with cortisol (n= 4; 2-3 mg kg(-1) d(-1)i.v.; Premature Cortisol) for 5 days. The Term Control group (n= 5) comprised fetuses that were surgically prepared at 130 dGA and infused with vehicle for 5 days prior to delivery (n= 2), or that received no surgery (n= 3). Under terminal anaesthesia, Premature Control and Premature Cortisol fetuses were delivered at 130 dGA and Term Control fetuses between 135 and 143 dGA. Following exsanguination under anaesthesia, fetal hearts were mounted in the Langendorff preparation, allowing measurement of left ventricular (LV) developed pressure and right ventricular (RV) developed pressure, heart rate (HR), coronary perfusion pressure and perfusate distribution to the myocardium. Cortisol infusion elevated fetal plasma cortisol concentrations to values similar to those measured close to term (45.0 +/- 7.1 ng ml(-1)). Advancing gestational age, but not cortisol treatment, enhanced fetal LV developed pressure, RV developed pressure and HR responses to carbachol (P < 0.05). Advancing gestational age, but not cortisol treatment, suppressed fetal LV developed pressure, RV developed pressure and HR responses to isoprenaline (P < 0.05). Maximum doses of either carbachol or isoprenaline had no effect on coronary perfusate distribution. Changes in myocardial responsiveness to adrenergic and muscarinic cholinergic stimulation with advancing gestation provide mechanisms that contribute to the maturation of the cardiovascular system as the ovine fetus approaches term. These changes in myocardial responsiveness are not solely dependent on preparturient elevations in fetal plasma cortisol concentration.

Adrenergic beta-Agonists↗

PubMed2004

Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep.

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.

Acute Disease↗

PubMed2004

Effects of dexamethasone on the uterine and umbilical vascular beds during basal and hypoxemic conditions in sheep.

OBJECTIVE: The purpose of the study was to test the hypotheses that maternal treatment with dexamethasone leads to a reduction in basal umbilical blood flow and diminishes the fetal umbilical hemodynamic response to acute hypoxemic stress in sheep. STUDY DESIGN: While under general anesthesia, 23 ewes and their fetuses were instrumented with vascular catheters and transonic blood flow probes around a uterine and umbilical artery at 117 days of gestation (term, approximately 145 days). At 124 days, the ewes were injected intramuscularly with 2 doses of either dexamethasone (12 mg) or saline solution at 24-hour intervals. All animals experienced 2 episodes of hypoxemia during treatment (125+/-1 days) and after treatment (128+/-1 days). RESULTS: Maternal dexamethasone treatment caused a sustained increase in fetal arterial blood pressure (from 41+/-3 mm Hg to 45+/-3 mm Hg) and a transient fall in umbilical vascular conductance (from 6.2+/-0.9 mL. min(-1). [mm Hg](-1) to 5.4+/-0.7 mL. min(-1). [mm Hg](-1)). During both episodes of hypoxemia, there was a significant increase in umbilical blood flow in the controls, but not in the dexamethasone-treated animals. CONCLUSION: Maternal dexamethasone treatment with doses used in human clinical practice significantly decreased basal umbilical vascular conductance and prevented the normal increase in umbilical blood flow that is induced by acute hypoxemia in fetal sheep.

Acid-Base Equilibrium↗

PubMed2003

Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation.

This study examined the effects of dexamethasone treatment on basal hypothalamo-pituitary-adrenal (HPA) axis function and HPA responses to subsequent acute hypoxemia in the ovine fetus during late gestation. Between 117 and 120 days (term: approximately 145 days), 12 fetal sheep and their mothers were catheterized under halothane anesthesia. From 124 days, 6 fetuses were continuously infused intravenously with dexamethasone (1.80 +/- 0.15 microg.kg(-1).h(-1) in 0.9% saline at 0.5 ml/h) for 48 h, while the remaining 6 fetuses received saline at the same rate. Two days after infusion, when dexamethasone had cleared from the fetal circulation, acute hypoxemia was induced in both groups for 1 h by reducing the maternal fraction of inspired O2. Fetal dexamethasone treatment transiently lowered fetal basal plasma cortisol, but not ACTH, concentrations. However, 2 days after treatment, fetal basal plasma cortisol concentration was elevated without changes in basal ACTH concentration. Despite elevated basal plasma cortisol concentration, the ACTH response to acute hypoxemia was enhanced, and the increment in plasma cortisol levels was maintained, in dexamethasone-treated fetuses. Correlation of fetal plasma ACTH and cortisol concentrations indicated enhanced cortisol output without a change in adrenocortical sensitivity. The enhancements in basal cortisol concentration and the HPA axis responses to acute hypoxemia after dexamethasone treatment were associated with reductions in pituitary and adrenal glucocorticoid receptor mRNA contents, which persisted at 3-4 days after the end of treatment. These data show that prenatal glucocorticoids alter the basal set point of the HPA axis and enhance HPA axis responses to acute stress in the ovine fetus during late gestation.

Acid-Base Equilibrium↗

PubMed2003

Cardiovascular and endocrine responses to acute hypoxaemia during and following dexamethasone infusion in the ovine fetus.

This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is approximately 145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 +/- 1 dGA, half of the fetuses (n = 13) were continuously infused I.V. with dexamethasone for 48 h at a rate of 2.06 +/- 0.13 microg kg-1 h-1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 +/- 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 +/- 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin responses were enhanced, whilst the prolonged bradycardia and augmented plasma NPY responses persisted. These data show that fetal treatment with dexamethasone modifies the pattern and magnitude of fetal cardiovascular responses to acute oxygen deprivation. Modifications to different mechanisms mediating the fetal defence responses to acute hypoxaemia that occur during dexamethasone treatment may reverse, persist or even become enhanced by 48 h following the treatment period.

Acid-Base Equilibrium↗

PubMed2003

Developmental regulation of hepatic and renal gluconeogenic enzymes by thyroid hormones in fetal sheep during late gestation.

Tissue glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) activities were investigated in sheep fetuses after experimental manipulation of thyroid hormone status. Increments in hepatic and renal G6P and PEPCK activities seen between 127-130 and 140-145 days of gestation (term, 145 +/- 2 days) were abolished when the normal prepartum rise in plasma triiodothyronine (T3), but not cortisol, was prevented by fetal thyroidectomy (TX). At 127-130 days, hepatic and renal G6P, and renal PEPCK, activities were similar in intact and TX fetuses; however, hepatic PEPCK was increased by TX. At 140-145 days, tissue G6P and PEPCK activities in TX fetuses were lower than in intact fetuses. In immature fetuses infused with cortisol (2-3 mg (kg body wt)-1 day-1) for five days, hepatic and renal enzyme activities were increased to those seen in mature fetuses near term. After five days of T3 infusion (8-12 microg (kg body wt)-1 day-1), G6P and PEPCK activities in the liver and kidney were greater than in saline-infused fetuses, but only renal G6P and PEPCK increased to the level seen close to term. Therefore, in fetal sheep, thyroid hormones are important for the prepartum rises in G6P and PEPCK activities in the liver and kidney and may mediate, in part, the maturational effects of cortisol.

Animals↗

PubMed2003

Effect of dexamethasone on pulmonary and renal angiotensin-converting enzyme concentration in fetal sheep during late gestation.

OBJECTIVES: The effect of dexamethasone on tissue angiotensin-converting enzyme (ACE) was investigated in fetal sheep. STUDY DESIGN: Pulmonary and renal ACE concentrations were measured in 16 sheep fetuses at between 127 and 131 days of gestation (term 145+/-2 days): 6 were untreated, whereas 10 were chronically catheterized and infused intravenously with either saline solution (0.9%, n=4) or dexamethasone (45-60 microg. kg(-1). d(-1), n=6) for the previous 2 days. The dexamethasone dose increased plasma dexamethasone to around one fifth of that measured in newborn human infants delivered after maternal dexamethasone treatment. RESULTS: Over the period of infusion, arterial blood pressure increased significantly in the dexamethasone (+6.8+/-1.5 mm Hg, P<.05) but not saline-treated fetuses (+1.6+/-0.6 mm Hg). At delivery, pulmonary ACE in the dexamethasone-infused fetuses (1.24+/-0.26 nmoles hippurate. min(-1). mg protein(-1)) was significantly greater than in the control fetuses (0.50+/-0.07 nmoles. min(-1). mg protein(-1), P<.005); renal ACE was unchanged by dexamethasone treatment. Overall, pulmonary ACE and blood pressure were correlated on the last day of infusion (r=0.70, P<.05). CONCLUSION: The rise in pulmonary ACE seen in dexamethasone-treated sheep fetuses may contribute, in part, to the glucocorticoid-induced increase in blood pressure.

Animals↗

PubMed2002

Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation.

This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 +/- 1 dGA, fetuses were infused with dexamethasone (2.06 +/- 0.13 microg kg(-1) h(-1) i.v.; n = 13) or saline (n = 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 +/- 1 (pre-infusion), 126 +/- 1 (during infusion) and 128 +/- 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 +/- 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 +/- 0.12 mmHg (ml min(-1))(-1) (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment.

Animals↗

PubMed2002

Postnatal cardiovascular function after manipulation of fetal growth by embryo transfer in the horse.

This study used between-breed embryo transfer in the horse to investigate the effects of maternal size and uterine capacity on fetal growth and postnatal cardiovascular and neuroendocrine functions. Equine embryos were transferred to establish eight Thoroughbred-in-Thoroughbred (TinT), seven Pony-in-Pony (PinP), five Thoroughbred-in-Pony (TinP) and eight Pony-in-Thoroughbred (PinT), pregnancies. Maternal and foal weights and placental microscopic area were measured at birth. At 6 days of postnatal life, arterial blood pressure and heart rate were monitored and blood samples were taken for hormone analysis before, during and after a 10 min period of nitroprusside-induced hypotension. Values for maternal and foal weights and placental area at birth were larger in TinT than in PinP pregnancies (P < 0.05). PinT pregnancies resulted in larger placentae and heavier foals relative to PinP (P < 0.05). TinP had smaller placentae and lighter foals relative to TinT (P < 0.05). Growth-enhanced (PinT) foals showed elevated basal arterial blood pressure and baroreflex threshold, reduced baroreflex sensitivity, diminished plasma catecholamine responses to acute stress, and increased cortisol responsiveness to ACTH. Conversely, growth-restricted (TinP) foals showed no change in basal arterial blood pressure, baroreflex threshold or adrenocortical responsiveness to ACTH, but had enhanced baroreflex sensitivity and augmented plasma catecholamine responses to acute stress. The data show that fetal growth acceleration as well as fetal growth restriction, resulting from between-breed embryo transfer in the horse, leads to altered postnatal regulation of blood pressure and the circulating concentrations of cortisol. These findings suggest that deviations in the pattern and rate of fetal growth both above and below the normal trajectory may influence cardiovascular function in postnatal life.

Adrenocorticotropic Hormone↗

PubMed2002

Adverse intrauterine conditions diminish the fetal defense against acute hypoxia by increasing nitric oxide activity.

BACKGROUND: The incidence of perinatal morbidity arising from birth hypoxia or asphyxia has not changed significantly in recent years despite marked improvements in labor management. Perinatal mortality in these circumstances may therefore reflect antenatal compromise and subsequent alteration of the fetal capacity to respond to episodes of hypoxia that may occur during labor. Hence, we have investigated the effects of fetal pre-exposure to a period of adverse intrauterine conditions on the mechanisms mediating the fetal defense response to a subsequent episode of acute hypoxia in sheep. METHODS AND RESULTS: Sixteen fetal sheep were chronically instrumented at 118+/-2 days for recording of blood pressure, heart rate, and femoral and umbilical blood flows. In 8 of these fetuses, umbilical blood flow was reduced by 30% for 3 days (between days 125 and 128). The remaining 8 fetuses acted as sham-operated controls. Between 2 and 7 days after umbilical cord/sham compression, all fetuses were exposed to 2 episodes of acute hypoxemia on separate days during infusion with either saline or treatment with a combination of N(G)-nitro-L-arginine methyl ester and sodium nitroprusside. We show that previous fetal exposure to a period of adverse intrauterine conditions, such as that induced by compression of the umbilical cord, elevates nitric oxide activity and results in a markedly diminished cardiovascular defense response to subsequent acute hypoxia. CONCLUSIONS: The data imply that pre-exposure to adverse antenatal conditions may render the fetus more susceptible to the acute hypoxia or asphyxia that can accompany relatively uncomplicated labor and delivery.

Animals↗