scholarly journals Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

2009 ◽  
Vol 296 (2) ◽  
pp. E300-E304 ◽  
Author(s):  
Luke C. Carey ◽  
Stephen B. Tatter ◽  
James C. Rose
Keyword(s):  
Signal Transduction ◽  
Arginine Vasopressin ◽  
Plasma Cortisol ◽  
Pituitary Cell ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Inositol 1,4,5 Trisphosphate ◽  
Sheep Fetus

Corticotrophs in the fetal sheep become increasingly responsive to arginine vasopressin (AVP) in late gestation. We previously reported that this may be due in part to corresponding increases in signal transduction (inositol 1,4,5-trisphosphate, IP3). These ontogenic changes are prevented by hypothalamo-pituitary disconnection (HPD), which also prevents fetal plasma cortisol concentrations from increasing in late gestation. This led us to hypothesize that cortisol is involved in mediating the changes in pituitary responsiveness. HPD was performed on fetal sheep at 120 days gestational age (dGA). Half of the HPD fetuses were infused with cortisol for 3 days beginning at 135–137 dGA (HPD+C). The remaining HPD fetuses and a group of sham-operated control fetuses were infused with saline. Pituitary cells were isolated and cultured. After 48 h, a subset of cells was stimulated with 100 nM AVP for 2 h, and the medium was collected for ACTH analysis. Another subset of cells was stimulated with 100 nM AVP for 30 min, and the formation of IP3 was determined. Plasma cortisol concentrations increased rapidly within the first 6 h after infusion (5.2 ± 1.9 to 29.7 ± 4.9 ng/ml) but did not increase thereafter. Cells from HPD+C and sham-operated fetuses secreted significantly more ACTH than those from HPD fetuses (% increase from control: 33.0 ± 8.8%, 47.9 ± 10.6%, and 11.9 ± 2.4%, respectively). IP3 formation was significantly increased in cells from HPD+C and sham-operated compared with HPD fetuses (% increase from control: 17.7 ± 4.4%, 18.9 ± 4.3%, and 4.6 ± 1.5%, respectively). These findings support the idea that cortisol plays a role in mediating the increase in pituitary responsiveness to AVP in the late-gestation fetal sheep.

scholarly journals Ontogeny and Effects of Hypothalamic Pituitary Disconnection on Formation of Inositol Trisphosphate in Fetal Sheep Pituitary Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1440-1444 ◽  
Author(s):  
Luke C. Carey ◽  
Stephen B. Tatter ◽  
James C. Rose
Keyword(s):  
Gestational Age ◽  
Plasma Cortisol ◽  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
The Impact ◽  
Pituitary Adrenal Axis ◽  
Sheep Fetus

In late gestation fetal sheep, the pituitary becomes increasingly responsive to stimulation by arginine vasopressin (AVP). This change appears to be one important factor mediating the plasma cortisol surge, a critical developmental event. It is not known precisely why pituitary corticotropes become more responsive at this time. In this study we examined the possibility that changes in second messenger generation [inositol trisphosphate (IP3)] are responsible. Two studies were undertaken. The first was an ontogeny study, where pituitaries were isolated from 100-, 120-, and 140-d gestational age (dGA) fetal sheep. Cells were cultured, stimulated with AVP, and the formation of IP3 assessed. The amount of IP3 generated increased with gestational age (percent increases from unstimulated controls were 4.6, 11.5, and 21.5 for 100, 120, and 140 dGA, respectively), with significant differences between the 140-dGA group and both earlier groups apparent. The second study examined the impact of 120-dGA hypothalamo-pituitary disconnection (HPD), which prevents corticotrope maturation, on responsiveness of pituitary cells isolated from 140-dGA fetuses. Cells were stimulated with AVP, and the formation of IP3 and secretion of ACTH were assessed. Significantly less IP3 was formed, and ACTH secreted in cells from HPD compared with control fetuses (IP3 and ACTH levels were 50% and 35% lower, respectively). Results from the HPD study demonstrate that the ontogenic changes in IP3 after AVP require an intact hypothalamic-pituitary-adrenal axis. These findings suggest that heightened second messenger generation may be a key reason for increased ACTH secretory responsiveness to AVP in the late gestation sheep fetus.

scholarly journals Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term

2002 ◽  
Vol 173 (1) ◽  
pp. 143-150 ◽  
Author(s):  
AJ Forhead ◽  
AL Fowden
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Thyroid Hormones ◽  
Plasma Cortisol ◽  
Experimental Manipulation ◽  
Late Gestation ◽  
Converting Enzyme ◽  
Fetal Sheep ◽  
Near Term ◽  
Sheep Fetus

In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T(3)). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 +/- 2 days), coincident with the prepartum rises in plasma cortisol and T(3). The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T(3), but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T(3) (8-12 microg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T(3) appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.

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.

Arginine vasopressin responses to hypoxia and hypercapnia in late-gestation fetal sheep

1991 ◽  
Vol 260 (6) ◽  
pp. R1077-R1081 ◽  
Author(s):  
H. Raff ◽  
C. W. Kane ◽  
C. E. Wood
Keyword(s):  
Arginine Vasopressin ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hypoxic Conditions ◽  
Arterial Ph ◽  
Hypercapnic Hypoxia ◽  
Per Se ◽  
Peripheral Arterial

The purpose of this study was to determine the interaction of hypoxia and hypercapnia in the control of arginine vasopressin (AVP) secretion in fetal sheep and to determine the role of the peripheral arterial chemoreceptors in that response. We measured the plasma AVP response to hypercapnia and/or hypoxia in catheterized intact or sinoaortic-denervated fetal sheep between 123 and 144 days of gestation. Ewes were exposed to the following inspired gases: two successive 30-min periods of normocapnic normoxia, 30 min of normocapnic normoxia followed by 30 min of normocapnic hypoxia, two successive 30-min periods of hypercapnic normoxia, or 30 min of hypercapnic normoxia followed by 30 min of hypercapnic hypoxia (i.e., asphyxia). Hypercapnia per se had no significant effect on fetal plasma AVP. Normocapnic hypoxia per se resulted in a significant increase in fetal plasma AVP. Although hypercapnia resulted in a significant acidemia, the decrease in arterial pH was more marked under hypoxic conditions. Hypercapnia/acidemia augmented the AVP response to hypoxia. Fetal sinoaortic denervation did not significantly attenuate any of the AVP responses. We conclude that hypercapnia augments the fetal AVP response to hypoxia and that the AVP response to neither normocapnic nor hypercapnic hypoxia is dependent on afferent information carried in the carotid sinus or aortic nerves.

scholarly journals Intrafetal Insulin-Like Growth Factor-I Infusion Stimulates Adrenal Growth But Not Steroidogenesis in the Sheep Fetus during Late Gestation

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5424-5432 ◽  
Author(s):  
J. T. Ross ◽  
I. C. McMillen ◽  
F. Lok ◽  
A. G. Thiel ◽  
J. A. Owens ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Adrenal Cortex ◽  
Plasma Cortisol ◽  
Zona Glomerulosa ◽  
Late Gestation ◽  
Zona Fasciculata ◽  
Synthetic Enzymes ◽  
Fetal Plasma ◽  
Igf I ◽  
Sheep Fetus

We investigated the effects of an intrafetal infusion of IGF-I on adrenal growth and expression of the adrenal steroidogenic and catecholamine-synthetic enzyme mRNAs in the sheep fetus during late gestation. Fetal sheep were infused for 10 d with either IGF-I (26 μg/kg·h; n = 14) or saline (n = 10) between 120 and 130 d gestation, and adrenal glands were collected for morphological analysis and determination of the mRNA expression of steroidogenic and catecholamine-synthetic enzymes. Fetal body weight was not altered by IGF-I infusion; however, adrenal weight was significantly increased by 145% after IGF-I infusion. The density of cell nuclei within the fetal adrenal cortex (the zona glomerulosa and zona fasciculata), and within the adrenaline synthesizing zone of the adrenal medulla, was significantly less in the IGF-I-infused fetuses compared with the saline-infused group. Thus, based on cell-density measurements, there was a significant increase in cell size in the zona glomerulosa and zona fasciculata of the adrenal cortex and in the adrenaline-synthesizing zone of the adrenal medulla. There was no effect of IGF-I infusion on the adrenal mRNA expression of the steroidogenic or catecholamine-synthetic enzymes or on fetal plasma cortisol concentrations. In summary, infusion of IGF-I in late gestation resulted in a marked hypertrophy of the steroidogenic and adrenaline-containing cells of the fetal adrenal in the absence of changes in the mRNA levels of adrenal steroidogenic or catecholamine-synthetic enzymes or in fetal plasma cortisol concentrations. Thus, IGF-I infusion results in a dissociation of adrenal growth and function during late gestation.

Regulation of lung liquid secretion by arginine vasopressin in fetal sheep

1990 ◽  
Vol 258 (1) ◽  
pp. R104-R111 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Gestational Age ◽  
Arginine Vasopressin ◽  
Plasma Cortisol ◽  
Fetal Lung ◽  
Inhibitory Effect ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Fetal Asphyxia ◽  
Lung Liquid ◽  
Secretion Rates

We have investigated the influence of gestational age on the inhibition of fetal lung liquid secretion by arginine vasopressin (AVP). In eight fetal sheep, lung liquid secretion rates were measured before and during infusion of AVP (300 mu.kg-1.h-1) at gestational ages between 110 and 148 days. During infusions, the concentration of AVP in fetal plasma increased from less than 8.7 +/- 0.2 pg/ml to 848.7 +/- 75.1 pg/ml. Fetal plasma epinephrine concentrations were not altered during AVP infusion. Infusions of AVP had no effect on fetal lung secretion before 135 days of gestation; they caused a 40.8% inhibition between 136 and 140 days, and at ages greater than 140 days induced an inhibition of 78.4%. In two ewes during labor, AVP infusion caused either a complete inhibition of secretion or reabsorption of lung liquid. The inhibitory effect of AVP increased in an exponential-like fashion with increasing gestational age and appeared to parallel the preparturient rise in fetal plasma cortisol concentrations. Our results indicate that AVP may be involved in the clearance of lung liquid at term and that AVP is unlikely to mediate the inhibitory effect of fetal asphyxia on lung liquid secretion, at least until after 135 days of gestation.

The effects of cortisol on the growth rate of the sheep fetus during late gestation

1996 ◽  
Vol 151 (1) ◽  
pp. 97-105 ◽  
Author(s):  
A L Fowden ◽  
J Szemere ◽  
P Hughes ◽  
R S Gilmour ◽  
A J Forhead
Keyword(s):  
Growth Rate ◽  
Plasma Glucose ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
The Body ◽  
Late Gestation ◽  
Crown Rump Length ◽  
Fetal Plasma ◽  
Normal Term ◽  
Sheep Fetus

Abstract Using indwelling crown–rump length (CRL)-measuring devices, the growth rate of sheep fetuses was monitored during late gestation and after experimental manipulation of fetal plasma cortisol by exogenous infusion and fetal adrenalectomy. In intact control fetuses, the increment in CRL declined progressively during the last 20–25 days of gestation: mean ± s.e.m. values fell from 5·5 ± 0·4 mm/day (n=12) at 21–25 days before delivery to 2·5 ± 0·3 mm/day (n=12) in the last 5 days before birth (P<0·01). These changes closely parallelled the normal prepartum increase in fetal plasma cortisol which rose from 19·3 ±3·3 nmol/l (n=10) at 21–25 days before birth to 177·4 ± 19·0 nmol/l (n=10) in the final 5 days before delivery (P<0·01). When this cortisol surge was prevented by fetal adrenalectomy, there was no decrease in CRL increment towards normal term: mean CRL increment in the 5 days before normal term (4·8 ± 0·6 mm/day, n=5) was similar to that observed at 21–25 days before term (4·7 ± 0·4 mm/day, n=5). At delivery at term, the body weight (4·116 ± 0·280 kg, n=5) and CRL (51·9 ± 1·7 cm, n=5) of the adrenalectomized fetuses were significantly greater than the corresponding values in their sham-operated controls (2·877 ± 0·070 kg and 47·1 ±1·6 cm, n=6, respectively). In contrast with the sham-operated controls, plasma glucose and insulin levels in the adrenal-ectomized fetuses decreased towards term. Infusion of cortisol into the preterm fetus for 5 days increased fetal plasma cortisol to term levels and decreased the CRL increment to a value (1·8 ± 0·5 mm/day, n=8) which was similar to that observed in untreated controls during the last 5 days before spontaneous delivery at term (2·1 ± 0·3 mm/day, n=6). There were no significant alterations in the fetal arterial concentrations of plasma glucose or insulin in response to fetal cortisol infusion. When all the data were combined irrespective of treatment or proximity to delivery, the fetal plasma concentrations of cortisol (P<0·001) and glucose (P<0·04), but not insulin (P>0·05), had a significant effect on the fetal CRL increment measured over 5-day periods during the last 25–30 days of gestation. These findings show that cortisol inhibits growth of the axial skeleton in the sheep fetus during late gestation. They also indicate that the prepartum cortisol surge may be responsible for the normal decline in fetal growth rate observed towards term in this species. Journal of Endocrinology (1996) 151, 97–105

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.

Corticosteroid-binding globulin (CBG) production by hepatic and extra-hepatic sites in the ovine fetus; effects of CBG on glucocorticoid negative feedback on pituitary cells in vitro

1995 ◽  
Vol 146 (1) ◽  
pp. 121-130 ◽  
Author(s):  
E T M Berdusco ◽  
K Yang ◽  
G L Hammond ◽  
J R G Challis
Keyword(s):  
Negative Feedback ◽  
Binding Capacity ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Ovine Fetus ◽  
Acth Release

Abstract Plasma cortisol levels increase in fetal sheep during late gestation and this is associated with an increase in plasma corticosteroid-binding globulin (CBG) concentrations. However, the relative tissue sources of plasma CBG, the ontogeny of its biosynthesis and glycoform composition have not been established in the ovine fetus. Therefore we examined whether changes in plasma corticosteroid binding capacity (CBC) in fetal sheep during late gestation were associated with different patterns of glycosylation and reflected changes in tissue CBG expression. Since free cortisol is considered the bioactive fraction, we measured changes in the percent and absolute free cortisol in fetal plasma during late gestation. In order to examine whether CBG alters cortisol negative feedback at the level of the fetal pituitary, we also examined the effect of exogenous CBG in mediating the glucocorticoid-induced suppression of basal and corticotrophin-releasing hormone (CRH)-stimulated ACTH release from fetal pituitary cells in culture. The mean free cortisol concentration in plasma was not different between days 15 and 20 prior to parturition, and between 5 and 10 days prepartum, although it did rise between these times. Plasma CBC in chronically catheterized fetuses rose from 23·3 ± 4·6 ng/ml at day 115 to 86·5 ± 20·8 ng/ml at term and then decreased rapidly after birth. Between day 125 and day 140 of pregnancy approximately 10% of fetal plasma CBG was retarded by Concanavalin-A chromatography. This proportion increased at birth and attained adult values of >70% by one month of age. By Northern blotting the relative levels of CBG mRNA in the fetal liver did not change between days 100 and 125, then increased significantly at day 140, but declined at term and in newborn lambs. CBG mRNA was undetectable in total RNA from lung, kidney, hypothalamus and placentomes, but was present in the fetal pituitary at days 125 and 140. Reverse transcription-PCR was used to confirm the presence of CBG mRNA in pituitary tissue from term fetuses. In cultures of term fetal pituitary cells, added CBG attenuated the cortisol- but not the dexamethasone-mediated suppression of basal and CRH-stimulated ACTH release. We conclude that in fetal sheep there is an increase in the corticosteroid binding capacity of plasma during late pregnancy which regulates, in part, free cortisol levels in the circulation. The liver is the major site of CBG biosynthesis in the fetus and at least until day 140 of gestation the rise in plasma CBC is associated with an increase in hepatic CBG mRNA levels. The fetal pituitary was also established as a site of CBG production. Output of ACTH by cultured pituitary cells was inhibited by cortisol and this effect was diminished in the presence of added CBG. This study supports a role for systemic CBG in modulating the availability of cortisol to the fetal pituitary and suggests an additional way of modifying feedback effects of cortisol at the pituitary through its own production of CBG. Journal of Endocrinology (1995) 146, 121–130

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.

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