Blood pressure and heart rate in the ovine fetus: ontogenic changes and effects of fetal adrenalectomy

1999 ◽  
Vol 276 (1) ◽  
pp. H248-H256 ◽  
Author(s):  
Nobuya Unno ◽  
Chi H. Wong ◽  
Susan L. Jenkins ◽  
Richard A. Wentworth ◽  
Xiu-Ying Ding ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Cortisol ◽  
Time Windows ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Long Term Study ◽  
Arterial Blood ◽  
Ovine Fetus

Ontogenic changes in baseline and 24-h rhythms of fetal arterial blood pressure (FABP) and heart rate (FHR) and their regulation by the fetal adrenal were studied in 18 fetal sheep chronically instrumented at 109–114 days gestation (GA). In the long-term study, FABP and FHR were continuously recorded from 120 days GA to spontaneous term labor (>145 days GA) in five animals. Peak times (PT) and amplitudes (Amp) of cosinor analysis were compared at 120–126, 127–133, and 134–140 days GA. Consistent, significant linear increases in FABP and linear decreases in FHR were observed in all fetuses. Significant 24-h rhythms in FABP and FHR were observed during all the time windows. In the adrenalectomy study, to test the hypothesis that fetal cortisol plays a key role in cardiovascular maturation, fetal adrenals were removed in eight animals (ADX); sham fetal adrenalectomy was performed on five animals (Con). Cortisol (4 μg/min) was infused intravenously in four ADX fetuses from day 7postsurgery for 7 days (ADX+F). No significant changes in PT and Amp in FABP and FHR were observed. Plasma cortisol levels remained low in Con and ADX fetuses (<4.9 ng/ml). Cortisol infusion increased fetal plasma cortisol to 22.3 ± 3.2 ng/ml (mean ± SE) on day 13 in ADX+F fetuses. FABP increased in control and ADX+F but not ADX fetuses; FHR decreased in control and ADX but rose in ADX+F fetuses. These results suggest that, in chronically instrumented fetal sheep at late gestation, 1) increases in FABP and decreases in FHR are maintained consistently from 120 to 140 days GA, with distinct 24-h rhythms, the PT and Amp of which remain unchanged, and 2) the physiological increase in FABP is dependent on the fetal adrenal; bilateral removal of the fetal adrenals does not prevent the ability of cortisol to produce a sustained increase in FABP.

Effects of fetal ovine adrenalectomy on sympathetic and baroreflex responses at birth

2002 ◽  
Vol 283 (2) ◽  
pp. R460-R467 ◽  
Author(s):  
Jeffrey L. Segar ◽  
Timothy Van Natta ◽  
Oliva J. Smith
Keyword(s):  
Plasma Cortisol ◽  
Late Gestation ◽  
Renal Nerve ◽  
Baroreflex Control ◽  
Fetal Sheep ◽  
Cesarean Section Delivery ◽  
Fetal Plasma ◽  
Arterial Blood ◽  
Baroreflex Function ◽  
Before And After

Studies were performed to test the hypothesis that the absence of adrenal glucocorticoids late in gestation alters sympathetic and baroreflex responses before and immediately after birth. Fetal sheep at 130–131 days gestation (term 145 days) were subjected to bilateral adrenalectomy before the normal prepartum increase in plasma cortisol levels. One group of fetuses ( n = 5) received physiological cortisol replacement with a continuous infusion of hydrocortisone (2 mg · day−1 · kg−1 for 10 days), whereas the other group received 0.9% NaCl vehicle ( n = 5). All animals underwent a second surgery 48 h before the study for placement of a renal nerve recording electrode. Heart rate (HR), mean arterial blood pressure (MABP), renal sympathetic nerve activity (RSNA), and baroreflex control of HR and RSNA were studied before and after cesarean section delivery. At the time of study (140–141 days gestation), fetal plasma cortisol concentration was undetectable in adrenalectomized (ADX) fetuses and 58 ± 9 ng/ml in animals receiving cortisol replacement (ADX + F). Fetal and newborn MABP was significantly greater in ADX + F relative to ADX animals. One hour after delivery, MABP increased 13 ± 3 mmHg and RSNA increased 91 ± 12% above fetal values in ADX + F (both P < 0.05) but remained unchanged in ADX lambs. The midpoint pressures of the fetal HR and RSNA baroreflex function curves were significantly greater in ADX + F (54 ± 3 and 56 ± 3 mmHg for HR and RSNA curves, respectively) than ADX fetuses (45 ± 2 and 46 ± 3 mmHg). After delivery, the baroreflex curves reset toward higher pressure in ADX + F but not ADX lambs. These results suggest that adrenal glucocorticoids contribute to cardiovascular regulation in the late-gestation fetus and newborn by modulating arterial baroreflex function and sympathetic activity.

Ovine fetal adrenal gland and cardiovascular function

1988 ◽  
Vol 254 (4) ◽  
pp. R706-R710 ◽  
Author(s):  
N. D. Ray ◽  
C. S. Turner ◽  
N. M. Rawashdeh ◽  
J. C. Rose
Keyword(s):  
Heart Rate ◽  
Adrenal Gland ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Cardiovascular Function ◽  
Late Gestation ◽  
Arterial Blood ◽  
Significant Difference ◽  
Ovine Fetus ◽  
Ovine Fetal

Given the necessity of the adrenal gland in maintaining cardiovascular function in adults of various species, these experiments were conducted to determine if fetal bilateral adrenalectomy results in altered resting heart rate, hypotension, and decreased basal blood volume as well as a diminished ability of the fetus to maintain arterial pressure and restore blood volume in response to hemorrhage. We studied heart rate, arterial blood pressure, and blood volume changes in response to hemorrhage of 20% of blood volume at 2%/min in seven adrenalectomized and six intact chronically cannulated unanesthetized lambs between 119 and 133 days of gestation. Blood volumes and percent restitution of shed volume were determined using 51Cr-tagged red blood cells and changes in hematocrit. There was no significant difference between groups in basal heart rate, mean arterial pressure, hematocrit, and blood volume. The two groups were similar to hemorrhage-induced changes in these and restitution of volume. Therefore, fetal adrenal glands are not necessary for basal cardiovascular function or regulation subsequent to moderate hemorrhage in the late gestation ovine fetus.

Divergent changes in plasma ACTH and pituitary POMC mRNA after cortisol administration to late-gestation ovine fetus

1998 ◽  
Vol 274 (3) ◽  
pp. E417-E425 ◽  
Author(s):  
T. M. Jeffray ◽  
S. G. Matthews ◽  
G. L. Hammond ◽  
J. R. G. Challis
Keyword(s):  
Plasma Cortisol ◽  
Late Gestation ◽  
Pars Intermedia ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Negative Feedback Regulation ◽  
Fetal Sheep ◽  
Pomc Mrna ◽  
Free Cortisol ◽  
Ovine Fetus

Plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH) rise in the late-gestation sheep fetus at approximately the same time as there is an increase in the plasma levels of corticosteroid- binding globulin (CBG). We hypothesized that intrafetal cortisol infusion during late pregnancy would stimulate an increase in fetal plasma CBG, which in turn would bind cortisol and diminish glucocorticoid negative-feedback regulation of the fetal pituitary, leading to an increase in plasma ACTH concentrations. Cortisol was infused into chronically catheterized fetal sheep beginning at 126.1 ± 0.5 days of gestation and continued for 96 h. Control fetuses were infused with saline. In cortisol-infused fetuses, the plasma cortisol concentrations rose significantly from control levels (4.4 ± 0.6 ng/ml) to 19.3 ± 3.1 ng/ml within 24 h and remained significantly elevated throughout the infusion period. Plasma immunoreactive (ir) ACTH concentrations were significantly elevated in cortisol-infused fetuses within 24–48 h and remained significantly higher than in controls throughout the 96-h experimental period. Plasma free cortisol concentrations increased 10-fold and remained significantly elevated in cortisol-infused animals, despite a rise in plasma corticosteroid-binding capacity. Levels of pituitary proopiomelanocortin (POMC) mRNA in the fetal pars distalis and pars intermedia were 96 and 38% lower, respectively, after 96 h of cortisol infusion. Therefore physiological elevations of plasma cortisol, in the late-gestation ovine fetus, lead to increases in mean plasma irACTH concentrations, but this is not associated with increases in fetal pituitary POMC mRNA levels.

Prevention of hypoinsulinemia modifies catecholamine effects in fetal sheep

2000 ◽  
Vol 278 (5) ◽  
pp. R1171-R1181 ◽  
Author(s):  
John M. Bassett ◽  
Clifford Hanson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Insulin Secretion ◽  
Metabolic Activity ◽  
Plasma Glucose ◽  
Insulin Infusion ◽  
Prolonged Infusion ◽  
Fetal Sheep ◽  
Intravenous Insulin ◽  
Arterial Blood

Increased epinephrine (Epi) and norepinephrine (NE) production plays an important role in fetal adaptation to reduced oxygen and/or nutrient availability, inhibiting insulin secretion and slowing growth to support more essential processes. To assess the importance of hypoinsulinemia for the efficacy of catecholamines, normoinsulinemia was restored by intravenous insulin infusion (0.18 mU ⋅ kg− 1 ⋅ min− 1) during prolonged infusion of either Epi (0.25–0.35 μg ⋅ kg− 1 ⋅ min− 1for 12 days, n = 7) or NE (0.5–0.7 μg ⋅ kg− 1 ⋅ min− 1for 7 days, n = 6) into normoxemic fetuses in twin-pregnant ewes, from 125–127 days of gestation. Insulin infusion for 8 days during Epi infusion or for 4 days during NE infusion decreased arterial blood pressure, O2 content, and plasma glucose, but increased heart rate significantly (all P <0.05), despite continuation of Epi or NE infusion. Cessation of insulin infusion reversed these changes. Estimated growth of fetuses infused with insulin during Epi or NE infusion (55 ± 13.9 and 83 ± 15.2 g/day) did not differ significantly from that of untreated controls (72 ± 15.4 g/day, n = 6). Growth of selected muscles and hindlimb bones was not altered either. Restoration of normoinsulinemia evidently counteracts the redistribution of metabolic activity and decreased anabolism brought about by Epi or NE in the fetus. Inhibition of insulin secretion by Epi and NE, therefore, appears essential for the efficacy of catecholamine action in the fetus.

Sinoaortic denervation attenuates the reflex responses to hypotension in fetal sheep

1989 ◽  
Vol 256 (5) ◽  
pp. R1103-R1110 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Heart Rate ◽  
Fetal Heart ◽  
Carotid Sinus ◽  
Late Gestation ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Venae Cavae ◽  
Afferent Fibers ◽  
Vascular Catheters

Hypotension in fetal sheep stimulates reflex decreases in heart rate and increases in the secretion of several hormones, including adrenocorticotropin (ACTH), cortisol, vasopressin, and renin. However, little is known about the afferent limb(s) of the reflex(es) controlling these responses. Fetal sheep between 122 and 134 days gestation were prepared with chronic vascular catheters, intravascular balloon-tipped catheters, and amniotic fluid catheters. Seven fetal sheep were also subjected to sinoaortic denervation, and nine remained intact. After recovery from surgery for 2-5 days, fetuses were subjected to a 10-min period of hypotension produced by vena caval obstruction, produced by inflation of balloons in the superior and inferior venae cavae. Vena caval obstruction produced decreases in fetal heart rate and increases in fetal plasma ACTH, vasopressin, and renin activity, which were related to the degree of hypotension. Prior sinoaortic denervation attenuated all of these responses. It is concluded that afferent fibers in the carotid sinus and/or aortic depressor nerves mediate part of the heart rate, ACTH, vasopressin, and renin responses to vena caval obstruction in late-gestation fetal sheep.

Effects of increased cortisol concentration on ovine fetal leucine kinetics and protein metabolism

1995 ◽  
Vol 268 (6) ◽  
pp. E1114-E1122 ◽  
Author(s):  
J. R. Milley
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Plasma Cortisol ◽  
Cortisol Concentration ◽  
Late Gestation ◽  
Fetal Plasma ◽  
Plasma Cortisol Concentration ◽  
Arterial Blood ◽  
Leucine Kinetics ◽  
Ovine Fetal

Fetal protein accretion decreases as gestation progresses, primarily because protein synthesis decreases. Also, glucocorticoid primarily because protein synthesis decreases. Also, glucocorticoid concentrations increase late in gestation, and restraint of growth is one of the most consistently noted effects of glucocorticoids. Therefore, this study was done to determine whether fetal protein accretion is decreased by increased cortisol concentration and whether such an effect might be due to decreased protein synthesis or increased proteolysis. Six days after surgery, fetal leucine and protein metabolism was measured in eight pregnant ewes (114-119 days of gestation) at normal and elevated cortisol concentrations. Arterial blood leucine concentration, fetal leucine disposal rate, and exogenous leucine uptake were unaffected by cortisol infusion. Fetal leucine decarboxylation, however, increased by 19% (P < 0.001). Increased fetal cortisol concentration increased fetal proteolysis by 11% (P < 0.001) but did not affect the use of leucine for protein synthesis. Consequently, fetal protein accretion fell by 34% (P < 0.002). We conclude that increased fetal plasma cortisol concentration increases fetal proteolysis, thereby decreasing the rate of fetal protein accretion, an effect different from the decreased protein synthesis reported in late gestation.

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

2005 ◽  
Vol 289 (4) ◽  
pp. R1006-R1014 ◽  
Author(s):  
Kai Chen ◽  
Luke C. Carey ◽  
Nancy K. Valego ◽  
Jingfang Liu ◽  
James C. Rose
Keyword(s):  
Thyroid Hormone ◽  
Receptor Expression ◽  
Late Gestation ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Active Renin ◽  
Arterial Blood

Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward term. At the same time, fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart, and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately before necropsy (∼137 dGA), fetuses were infused with isoproterenol and the hemodynamic responses were noted. TX significantly decreased plasma thyroid hormone concentrations and renal renin mRNA and renal active renin levels but did not change fetal plasma active renin levels. TX decreased both angiotensin II receptor subtype 1 (AT1) mRNA and protein levels in kidney and lung but not in the left ventricle. TX also was associated with increased ANG II receptor subtype 2 (AT2) mRNA and protein at the 44-kDa band in kidney, whereas AT2 protein was decreased at the 78-kDa level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late-gestation fetal sheep.

Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep

2006 ◽  
Vol 291 (2) ◽  
pp. E214-E220 ◽  
Author(s):  
Luke C. Carey ◽  
Yixin Su ◽  
Nancy K. Valego ◽  
James C. Rose
Keyword(s):  
Regulatory Protein ◽  
Late Gestation ◽  
Mrna Levels ◽  
Acth Stimulation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Arterial Blood ◽  
Acth Receptor ◽  
Underlying Mechanisms

The late-gestation plasma cortisol surge in the sheep fetus is critical for stimulating organ development and parturition. Increased adrenal responsiveness is one of the key reasons for the surge; however, the underlying mechanisms are not fully understood. Our recent studies suggest that ACTH-mediated increased expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) may play a role in enhancing responsiveness. Hence, we examined effects of ACTH infusion in fetal sheep on mRNA expression of these two mediators of adrenal responsiveness and assessed the functional consequences of this treatment in vitro. Fetuses of ∼118 and 138 days of gestational age (dGA) were infused with ACTH-(1–24) for 24 h. Controls received saline infusion. Arterial blood was sampled throughout the infusion. Adrenals were isolated and analyzed for ACTH-R and StAR mRNA, or cells were cultured for 48 h. Cells were stimulated with ACTH, and medium was collected for cortisol measurement. Fetal plasma ACTH and cortisol concentrations increased over the infusion period in both groups. ACTH-R mRNA levels were significantly higher in ACTH-infused fetuses in both the 118 and 138 dGA groups. StAR mRNA increased significantly in both the 118 and 138 dGA groups. Adrenal cells from ACTH-infused fetuses were significantly more responsive to ACTH stimulation in terms of cortisol secretion than those from saline-infused controls. These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH-R and StAR mRNA and are coupled to heightened adrenal responsiveness.

Long-term hypoxia increases leptin receptors and plasma leptin concentrations in the late-gestation ovine fetus

2006 ◽  
Vol 291 (5) ◽  
pp. R1406-R1413 ◽  
Author(s):  
Charles A. Ducsay ◽  
Kim Hyatt ◽  
Malgorzata Mlynarczyk ◽  
Kanchan M. Kaushal ◽  
Dean A. Myers
Keyword(s):  
Leptin Receptor ◽  
Placental Tissue ◽  
Late Gestation ◽  
Leptin Receptors ◽  
Fetal Plasma ◽  
Arterial Blood ◽  
Ovine Fetus ◽  
Plasma Leptin ◽  
Leptin Expression

This study was designed to test the hypothesis that long-term hypoxia (LTH) increases fetal plasma leptin and fetal adipose or placental leptin expression and alters hypothalamic and adrenocortical leptin receptor (OB-R) expression. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 to ∼130 days of gestation. Reduced Po2 was maintained in the laboratory by nitrogen infusion through a maternal tracheal catheter. On day 132, normoxic control and LTH fetuses underwent surgical implantation of vascular catheters ( n = 6 for each group). Five days after surgery, maternal and fetal arterial blood samples were collected for leptin, insulin, and glucose analysis. Placental tissue, periadrenal fat, and fetal hypothalami and adrenal glands were collected from additional control ( n = 7) and LTH ( n = 8) fetuses for analysis of leptin mRNA by quantitative, real-time, RT-PCR (qRT-PCR). There was a significant ( P < 0.03) elevation in fetal plasma leptin in the LTH fetuses (3.5 ± 0.7 ng/ml) vs. control (1.1 ± 0.1 ng/ml). There were no differences in either glucose or insulin concentrations between the two groups. Periadrenal adipose leptin mRNA was significantly higher in the LTH group compared with control, as was placental leptin expression. The levels of leptin mRNA in adipose were ∼70 times higher vs. placenta. LTH significantly reduced expression of OB-Ra (short-isoform) in the hypothalamus ( P = 0.0156), while resulting in a significant increase in adrenal OB-Rb (long-form) expression ( P < 0.03). Our data suggest that leptin is a hypoxia-inducible gene in the ovine fetus and OB-R expression is altered by LTH. These changes may be responsible in part, for our previously observed alterations in fetal hypothalamic-pituitary-adrenal function following LTH.

Is baroreflex control of sympathetic activity and heart rate active in the preterm fetal sheep?

2009 ◽  
Vol 296 (3) ◽  
pp. R603-R609 ◽  
Author(s):  
Lindsea C. Booth ◽  
Simon C. Malpas ◽  
Carolyn J. Barrett ◽  
Sarah-Jane Guild ◽  
Alistair J. Gunn ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Pressure Control ◽  
Autonomic Response ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Fetal Sheep ◽  
Arterial Blood

The arterial baroreflex is a fundamental reflex that buffers rapid changes in arterial blood pressure (BP) via regulation of the heart rate and sympathetic nerve activity to the vasculature. In adults a sigmoidal relationship between BP and both heart rate and sympathetic nerve activity is well documented. Its role in blood pressure control before birth is unclear. Preterm babies have a high incidence of low BP, especially in the first few days of life, which could be related, in part, to immaturity of the baroreflex. In the present study, we investigated the baroreflex control of fetal heart rate and renal sympathetic nerve activity (RSNA) in preterm fetal sheep in utero (102 ± 1 days of gestation; term 140 days). Phenylephrine was associated with a significant increase in BP from 38 ± 2 to 58 ± 3 mmHg and a decrease in heart rate (HR) from 177 ± 4 to 116 ± 8 beats per minute (bpm). Sodium nitroprusside was associated with a significant fall in BP from 38 ± 2 to 26 ± 1 mmHg and an increase in HR from 182 ± 4 to 274 ± 8 bpm. However, the time between the 50% changes in BP and HR was significantly greater after hypotension than hypertension (31 ± 8 s vs. 14 ± 5 s, P < 0.05). No significant changes in RSNA occurred with either stimulus. This suggests that there are different maturational tempos for the components of the central autonomic response to altered blood pressure.

Sign in / Sign up

Export Citation Format

Share Document