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Biomedical subjects

A J Forhead

Publications and source records attributed to A J Forhead.

At least 37 records · Page 2Linked to original sources
PubMed2002

Thyroid hormones and the mRNA of the GH receptor and IGFs in skeletal muscle of fetal sheep.

Thyroid hormones are required for the normal development of skeletal muscle in utero, although their mechanism of action is poorly understood. The present study examined the effects of the thyroid hormones on the gene expression of the growth hormone receptor (GHR) and the insulin-like growth factors (IGFs) IGF-I and IGF-II, in skeletal muscle of fetal sheep during late gestation (term 145 +/- 2 days) and after manipulation of plasma thyroid hormone concentration. Thyroidectomy at 105-110 days of gestation suppressed muscle GHR and IGF-I gene expression in fetuses studied at 127-130 and 142-145 days. Muscle GHR mRNA abundance remained unchanged with increasing gestational age in intact and thyroidectomized fetuses. In the intact fetuses, a decrease in muscle IGF-I gene expression was observed between 127-130 and 142-145 days, which coincided with the normal prepartum surges in plasma cortisol and triiodothyronine (T3). At 127-130 days, downregulation of muscle IGF-I mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2-3 mg x kg(-1) x day(-1) iv), which increased plasma cortisol and T3 concentrations to values seen near term. However, increasing plasma T3 alone by an infusion of T3 for 5 days (8-12 microg x kg(-1) x day(-1) iv) in intact fetuses at this age had no effect on GHR or IGF-I gene expression in skeletal muscle. In the thyroidectomized fetuses, no additional change in the low level of muscle IGF-I mRNA abundance was seen with increasing gestational age, but at 127-130 days, IGF-I gene expression was reduced further when plasma cortisol and T3 concentrations were increased by exogenous cortisol infusion. Muscle IGF-II mRNA abundance was not affected by thyroidectomy, gestational age, or exogenous hormone infusion. These findings show, in the sheep fetus, that thyroid hormones may influence the growth and development of skeletal muscle via changes in the local activity of the somatotrophic axis.

Animals↗
PubMed2002

Plasma leptin concentration in fetal sheep during late gestation: ontogeny and effect of glucocorticoids.

The ontogeny and developmental control of plasma leptin concentration in the fetus are poorly understood. The present study investigated plasma leptin concentration in chronically catheterized sheep fetuses near term, and in neonatal and adult sheep. The effect of glucocorticoids on plasma leptin in utero was examined by fetal adrenalectomy and exogenous cortisol or dexamethasone infusion. In intact, untreated fetuses studied between 130 and 140 d (term, 145 +/- 2 d), plasma leptin concentration increased in association with the prepartum cortisol surge. Positive relationships were observed between plasma leptin in utero and both gestational age and plasma cortisol. Plasma leptin was also inversely correlated with fetal p(a)O(2). The ontogenic rise in plasma leptin was abolished by fetal adrenalectomy. In intact fetuses at 123-127 d, plasma leptin was increased by infusions of cortisol (3-5 mg kg(-1)d(-1), +127 +/- 21%) for 5 d and dexamethasone (45-60 microg kg(-1)d(-1), +268 +/- 61%) for 2 d. However, the cortisol-induced rise in plasma leptin was transient; by the fifth day of infusion, plasma leptin was restored to within the baseline range. These findings show that, in the sheep fetus, an intact adrenal gland is required for the normal ontogenic rise in plasma leptin near term. Furthermore, fetal treatment with exogenous and endogenous glucocorticoids increases circulating leptin concentration in utero.

Adrenalectomy↗
PubMed2002

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol.

The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 beta-HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 beta-HSD2 activity decreased between 128-132 days and term (approximately 145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128--132 days of gestation reduced placental 11 beta-HSD2 activity to term values. In contrast, 11 beta-HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 beta-HSD2 activity, expressed both on a weight-specific basis and per mg placental protein. Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 beta-HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2002

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

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.

Animals↗
PubMed2001

Ontogeny of pulmonary and renal angiotensin-converting enzyme in pigs.

The present study investigated the ontogeny of pulmonary and renal angiotensin-converting enzyme (ACE) in foetal and postnatal pigs, and examined the effect of cortisol on tissue ACE in utero. Data were compared with those in sheep at similar ages. Under anaesthesia, tissues and umbilical blood were collected from pig foetuses between 81-115 days of gestation (term, 115+/-2 days). Twelve foetuses delivered at 97+/-2 days were infused with saline or cortisol (3-6 mgkg(-1)day(-1)) using osmotic mini-pumps implanted 6 days previously. Tissues were collected from newborn piglets, and from pigs at 2-4 weeks, 10-12 weeks and 10-12 months of age. Unlike in sheep, gestational age and exogenous cortisol had no effect on pulmonary or renal ACE in pigs. After birth, pulmonary ACE decreased to a nadir at 2-4 weeks and remained low thereafter. Renal ACE increased between 10-12 weeks and 10-12 months. Postnatal changes in tissue ACE may have consequences for cardiovascular, pulmonary and renal function in pigs.

Animals↗
PubMed2001

Regulation of glucogenesis by thyroid hormones in fetal sheep during late gestation.

The effects of thyroid hormone deficiency in utero on the fetal glucogenic capacity were investigated by measuring glucose production and hepatic levels of glycogen and gluconeogenic enzymes in normal sheep fetuses in the fed and fasted states during late gestation and in those made thyroid hormone deficient by fetal thyroidectomy (TX). In the fed state, fetal TX had no effect on glucose uptake, utilisation or production by the fetus. It also had no apparent effect on the glycogen content or activities of the key gluconeogenic enzymes in the fetal liver. In addition, fetal plasma concentrations of insulin, cortisol, adrenaline or noradrenaline were unaffected by fetal TX in the fed state. In contrast, the rates of fetal O(2) consumption and CO(2) production per kilogram fetal bodyweight were significantly lower in TX than in intact fetuses in the fed state (P<0.05). TX prevented fetal glucose production in response to maternal fasting for 48 h. It also abolished the normal decreases in the fetal glucose carbon oxidation fraction, the rate of CO(2) production from glucose carbon and in the fraction of the umbilical O(2) uptake used for glucose carbon oxidation that occur during fasting in intact fetuses. At the end of the fast, plasma noradrenaline concentrations and hepatic levels of glycogen, glucose 6-phosphatase, fructose diphosphatase and alanine aminotransferase were significantly lower in TX than in intact fetuses. These observations show that thyroid hormones are essential for glucogenesis in the sheep fetus during late gestation and suggest that these hormones act both on the hepatic glucogenic pathways and on the mechanisms activating glucogenesis in utero.

Alanine Transaminase↗
PubMed2000

Ontogenic and nutritionally induced changes in fetal metabolism in the horse.

1. Using the Fick principle and tracer methodology, the metabolic rates of chronically catheterized fetal foals (n = 24) were measured at different gestational ages during the second half of gestation and in response to maternal fasting for 36 h in late gestation (n = 4, term approximately 335 days). 2. Absolute rates of umbilical blood flow, fetal glucose utilization and umbilical uptake of oxygen (O2) and glucose increased from mid-gestation to 300 days and then plateauxed until term. The absolute rate of umbilical lactate uptake was significant after, but not before, 280 days of gestation. Weight specific rates of umbilical uptake and fetal utilization of glucose decreased progressively throughout the second half of gestation. 3. Weight specific rates of CO2 production from glucose carbon were also inversely correlated with gestational age. Umbilical lactate uptake per kilogram of fetus was lower after 320 days than between 281 and 300 days. In contrast, no gestational trends were observed in the weight specific rates of fetal O2 uptake and urea production. Glucose production by the fetal horse was negligible, even very close to term. 4. Maternal fasting for 36 h reduced the rate of umbilical uptake and utilization of glucose production but had no effect on the rates of endogenous glucose production and umbilical uptake of oxygen and lactate by the horse fetus. 5. The observations show that fetal metabolism is highly dependent on glucose in the horse compared to the sheep in mid- and late gestation. Different species therefore adopt different strategies in meeting the nutritional demands of the growing fetus during the second half of gestation.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Role of cortisol in the ontogenic control of pulmonary and renal angiotensin-converting enzyme in fetal sheep near term.

1. This study examined the ontogeny of angiotensin-converting enzyme (ACE) concentration in the lungs and kidneys of fetal, newborn and adult sheep, and investigated the effects of cortisol infusion on tissue and plasma ACE in the chronically catheterised ovine fetus. 2. Pulmonary and renal ACE in utero increased from 113 days of gestation towards term; peak tissue ACE concentrations were observed in fetuses studied at 143 days (term, 145 +/- 2 days). The high level of ACE seen in the fetal lungs close to term was maintained in the lambs and adult ewes whereas renal ACE decreased immediately after birth and rose to a maximal value in the adult ewes. In all groups of animals studied, higher mean concentrations of ACE were observed in the kidneys than in the lungs. Ontogenic increments in pulmonary and renal ACE in utero were coincident with the prepartum cortisol surge. In untreated and saline-infused fetuses, plasma cortisol correlated with both pulmonary (r = 0.83, P < 0.0001) and renal (r = 0.53, P < 0.01) ACE concentrations, irrespective of gestational age. 3. An intravenous infusion of cortisol (2-3 mg kg-1 day-1) at either 113 or 129 days raised plasma cortisol to the level seen near term and caused an increase in pulmonary ACE at both gestational ages. Pulmonary ACE concentration in the cortisol-infused fetuses at 129 days, but not at 113 days, was similar to that observed in the fetuses near term. In contrast, cortisol infusion had no effect on renal ACE concentration at either 113 or 129 days of gestation. Plasma ACE concentration was also increased by exogenous cortisol at 129 days. 4. Therefore, these findings suggest that the ontogenic rise in ACE concentration observed in the lungs of the sheep fetus near term is induced, at least in part, by the prepartum cortisol surge.

Animals↗
PubMed2000

Effect of cortisol on blood pressure and the renin-angiotensin system in fetal sheep during late gestation.

The effects of cortisol on blood pressure and the circulating components of the renin-angiotensin system (RAS) were investigated in sheep fetuses during late gestation and after exogenous cortisol infusion. Plasma cortisol concentration was greater in fetuses at 140 +/- 1 days of gestation (term 145 +/- 2 days) compared to those studied earlier in gestation (128 +/- 1 days), although, because of wide inter-animal variation, no differences were observed in blood pressure or plasma angiotensin II (AII), renin or angiotensinogen (Ao) concentrations. At 129 +/- 1 days of gestation, an infusion of cortisol for 5 days (2-3 mg kg(-1) day(-1) i.v.) increased plasma cortisol concentration to a value normally seen close to term. This rise in plasma cortisol was accompanied by increases in blood pressure and plasma concentrations of AII, renin and Ao. When observations from all fetuses were considered, plasma cortisol concentration correlated with plasma AII and renin, and blood pressure correlated with plasma cortisol and AII concentrations. Intravenous administration of an AII type 1 (AT(1))-specific receptor antagonist (3 mg kg(-1) GR138950) caused a reduction in blood pressure in all fetuses; the hypotensive response was greatest in fetuses studied near term and in the cortisol-treated fetuses. Overall, the magnitude of the hypotension induced by GR138950, and the concomitant rise in plasma renin, both correlated with the plasma cortisol concentration before GR138950 treatment. These findings show that, in the sheep fetus during late gestation, the RAS becomes more important in the maintenance of resting blood pressure when plasma cortisol concentration is elevated, whether endogenously or exogenously.

Angiotensin II↗
PubMed2000

Control of ovine hepatic growth hormone receptor and insulin-like growth factor I by thyroid hormones in utero.

By use of RNase protection assays, hepatic growth hormone receptor (GHR) and insulin-like growth factor I (IGF-I) mRNA abundances were measured in sheep fetuses after experimental manipulation of fetal plasma thyroid hormone concentrations by fetal thyroidectomy (TX) and exogenous infusion of triiodothyronine (T(3)) and cortisol. TX abolished the normal prepartum rise in hepatic GHR abundance but had little effect on hepatic GHR gene expression at 127-130 days (term 145 +/- 2 days). By contrast, it upregulated basal IGF-I expression in immature fetal liver by increasing both Class 1 and Class 2 transcript abundance but had no further effects on IGF-I gene mRNA levels at 142-145 days. Raising plasma T(3) to prepartum values by exogenous infusion of either T(3) or cortisol into immature intact fetuses prematurely raised hepatic GHR and IGF-I mRNA abundances to values similar to those seen in intact fetuses at 142-145 days. In TX fetuses, cortisol infusion increased hepatic GHR mRNA but not total IGF-I mRNA abundance at 127-130 days. These findings show that thyroid hormones have an important role in the regulation of hepatic GHR and IGF-I gene expression in fetal sheep during late gestation and suggest that T(3) mediates the maturational effects of cortisol on the hepatic somatotropic axis close to term.

Animals↗
PubMed2000

Low doses of dexamethasone suppress pituitary-adrenal function but augment the glycemic response to acute hypoxemia in fetal sheep during late gestation.

Despite the widespread use of antenatal glucocorticoid therapy in obstetric practice, little is known about the effects of synthetic glucocorticoids on the fetal capacity to respond to episodes of acute hypoxemia, such as may occur during labor and delivery. This study investigated the effects of prolonged fetal exposure to low concentrations of dexamethasone on the fetal ACTH, cortisol, and glycemic responses to an episode of acute hypoxemia during the period of dexamethasone treatment in sheep. At 118 d of gestation (term is approximately 145 d), 11 fetal sheep had catheters implanted under halothane anesthesia. From 124 d, five fetuses were infused i.v. continuously with dexamethasone (1.80 +/- 0.15 microg x kg(-1) x h(-1) in 0.9% saline at 0.5 mL/h) for 48 h, and the other six fetuses received saline solution i.v. at the same rate. At 45 h of infusion, acute hypoxemia was induced in all fetuses for 1 h by reducing the maternal inspired fraction of oxygen. During glucocorticoid treatment, fetal plasma dexamethasone concentrations increased to 3.9 +/- 0.2 nM by 24 h and remained elevated for the rest of the infusion period. During hypoxemia, a similar fall in fetal arterial PO2 occurred in both saline-infused and dexamethasone-treated fetuses. In control fetuses, significant increases in plasma ACTH and cortisol concentrations and in blood glucose concentrations occurred during hypoxemia. Dexamethasone treatment prevented the increases in fetal plasma ACTH and cortisol, and augmented the blood glucose response, induced by hypoxemia. These data indicate that prolonged fetal exposure to low concentrations of dexamethasone suppresses pituitary-adrenal function, but augments the glycemic response, to acute hypoxemia in fetal sheep during late gestation.

Acid-Base Equilibrium↗
PubMed2000

Equine uteroplacental metabolism at mid- and late gestation.

Uptakes of oxygen, glucose and lactate by the gravid uterus, fetus and uteroplacental tissues were measured in chronically catheterized pregnant ponies and their fetuses at mid- and late gestation (term 335 days). Rates of O2 uptake by the gravid uterus, fetus and uteroplacental tissues were significant at both gestational ages and were 2- to 3-fold higher in late gestation than the mid-gestation values of 3338+/-794, 1352+/-258 and 2035 +/- 602 micromol min(-1), respectively (n = 4). Similarly, there were significant uptakes of glucose by the gravid uterus, fetus and uteroplacental tissues at both mid- and late gestation. However, unlike O2 uptake, glucose uptake by the uterus and uteroplacental tissues did not increase between mid- and late gestation. No significant uptakes or outputs of lactate were observed by the uterus or uteroplacental tissues at either gestational age, although there was a significant umbilical uptake of lactate in late but not mid-gestation. There was no change in the distribution of uterine O2 uptake between the fetus and uteroplacental tissues with increasing gestational age. The uteroplacental tissues accounted for about 50 % of the uterine O2 uptake at both gestational ages. In contrast, the proportion of the uterine glucose uptake used by the uteroplacental tissues decreased from 73.2+/-2.1 % (n = 5) at mid-gestation to 61.1+/-1.9 % (n = 4, P<0.02) in late gestation. The gestational changes in uteroplacental carbohydrate metabolism in the mare differ from those seen in the ewe and may have important consequences for the duration and outcome of pregnancy in the mare.

Animals↗
PubMed1999

Pancreatic alpha cell function in the fetal foal during late gestation.

Plasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term (approximately 335 days). Fetal alpha cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal alpha cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal pre-infusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper- or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic alpha cells are functional in utero but that they are unresponsive to variations in glycaemia until after birth.

Amino Acids↗
PubMed1998

Developmental changes in plasma angiotensin-converting enzyme concentration in fetal and neonatal lambs.

Relationships between plasma angiotensin-converting enzyme (ACE) and cortisol, and blood pressure were examined in chronically catheterized ewes and their fetuses during late gestation (111-141 days, term 145 +/- 2 days). Plasma ACE was also measured in non-pregnant adult ewes and in lambs over the first 5 weeks of life. In fetuses near term (136-141 days), plasma ACE was greater than in those studied earlier in gestation; overall, plasma ACE correlated with gestational age (r = 0.72). The ontogenic rise in plasma ACE was associated with prepartum increases in plasma cortisol (r = 0.67) and blood pressure (r = 0.66). No relationship was observed between plasma ACE and partial pressure of oxygen in utero. Peak plasma ACE concentration observed in fetuses near term was maintained in newborn lambs for 3 days after birth. By 2 weeks of postnatal age, plasma ACE had decreased to the value seen in non-pregnant adult ewes. Maternal plasma ACE was similar at all gestational ages studied, and was lower than that observed in non-pregnant ewes. Therefore, in the sheep fetus, plasma ACE increased towards term in association with the prepartum cortisol surge. Developmental changes in ACE activity may be partly responsible for the ontogenic rise in fetal blood pressure.

Age Factors↗
PubMed1998

Control of hepatic insulin-like growth factor II gene expression by thyroid hormones in fetal sheep near term.

The effects of thyroid hormones on hepatic insulin-like growth factor (IGF) II gene expression and their interaction with cortisol in the ontogenic control of this gene were investigated in fetal sheep during late gestation (term 145 +/- 2 days) and after experimental manipulation of fetal plasma hormone concentrations. In intact fetuses, a significant decrease in hepatic IGF-II mRNA abundance was observed between 127-130 and 142-145 days of gestation, which coincided with the normal prepartum rise in plasma cortisol and triiodothyronine (T3) concentrations. This ontogenic decline in hepatic IGF-II gene expression was abolished in fetuses in which the prepartum rise in plasma T3, but not cortisol, was prevented by fetal thyroidectomy. At 127-130 days, downregulation of hepatic IGF-II mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2-3 mg . kg-1 . day-1 iv). Plasma concentrations of cortisol and T3 in the cortisol-infused intact fetuses were increased to values seen close to term. Similar findings were observed in thyroidectomized fetuses, in which, despite thyroidectomy, cortisol infusion significantly increased plasma T3 concentrations and caused a premature decrease in hepatic IGF-II mRNA levels. However, in intact fetuses at 127-130 days, the increasing of T3 concentrations alone by exogenous T3 infusion (8-12 microg . kg-1 . day-1 iv for 5 days) had no effect on hepatic IGF-II mRNA levels. Overall, a decrease in hepatic IGF-II mRNA abundance was only observed in fetuses in which there were concurrent increases in plasma cortisol and T3 concentrations. When observations from all fetuses were considered, irrespective of gestational age or treatment, hepatic IGF-II mRNA levels were negatively correlated with plasma cortisol and T3 but not thyroxine concentrations. Partial correlation analysis of hepatic IGF-II, cortisol, and T3 values showed that the plasma concentration of cortisol in the fetus had the predominant effect on hepatic IGF-II mRNA abundance. These findings show that T3 may mediate, in part, the maturational effects of cortisol on hepatic IGF-II gene expression but that it is ineffective without a concomitant rise in fetal plasma cortisol. Hence, increased concentrations of both cortisol and T3 appear necessary to induce downregulation of hepatic IGF-II mRNA abundance in fetal sheep close to term.

Animals↗
PubMed1997

Glucose, lactate and oxygen metabolism in the fetal pig during late gestation.

Using [U-14C]glucose tracer, rates of umbilical uptake, utilization and production of glucose, and of CO2 production from glucose carbon, were measured in seven chronically catheterized fetal pigs, when the sow was in the fed state, between 100 and 113 days of gestation (term, 114 +/- 2 days). At the same time, rates of umbilical O2 and lactate uptake were determined in all seven fetuses by the Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization and CO2 production from glucose carbon were 38.4 +/- 4.2, 41.3 +/- 5.2 and 126.9 +/- 12.6 mumol min-1 (kg fetal body weight)-1, respectively (n = 7), No glucose production was therefore detected in the fetuses. Production of CO2 from glucose carbon accounted for 37.3 +/- 3.4% (n = 7) of the umbilical O2 uptake, which averaged 340 +/- 13 mumol min-1 kg-1 (n = 7). There was also significant umbilical lactate uptake in the fetal piglets when the sow was in the fed state (32.6 +/- 10.4 mumol min-1 kg-1, n = 7, P < 0.05). No significant changes in fetal glucose, O2 or lactate metabolism were observed with increasing age towards term. The fetal rates of glucose metabolism and of umbilical uptake of O2 and lactate were not correlated with fetal blood glucose level. Hence, glucose is used for both oxidative and non-oxidative metabolism in utero and is an important, although not the sole, source of carbon for metabolic processes in the fetal pig during late gestation.

Animals↗
PubMed1997

Changes in the maternal and fetal renin-angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition in pregnant sheep during late gestation.

The effects of maternal administration of either an angiotensin II type 1 (AT1) receptor antagonist (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) on the renin-angiotensin system (RAS) were investigated in chronically catheterized ewes and their fetuses during late gestation. From 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received daily i.v. injections of GR138950 (3 mg kg-1, n = 10 animals) or captopril (3 mg kg-1, n = 6) or an equivalent volume of vehicle solution (0.9% NaCl, n = 10). On the first day of treatment, plasma renin concentrations in the pregnant ewe increased within 2 h of administration of either GR138950 (median change followed by lower and upper quartiles (25%, 75%): +38.3 ng ml-1 h-1 (15.6, 80.7); P < 0.05) or captopril (+22.1 ng ml-1 h-1 (19.2, 28.8); P < 0.05). Maternal plasma concentrations of angiotensin II (AII) also increased by 871 pg ml-1 (555, 1340; P < 0.05) in the GR138950-treated ewes. In the fetuses of both groups of drug-treated animals, an increase in plasma renin concentration was observed within 2 h of maternal treatment with either GR138950 (+11.6 ng ml-1 h-1 (1.2, 18.6); P < 0.05) or captopril (+59.3 ng ml-1 h-1 (41.7, 74.6); P < 0.05). These short-term changes in circulating renin and AII concentrations observed in the pregnant ewe were sustained after 1 week of GR138950 administration. In addition, 1 week of GR138950 treatment decreased plasma angiotensinogen (Ao) concentrations in both the ewe (-0.36 microgram ml-1 (-0.58, -0.16); P < 0.05) and the fetus (-0.43 microgram ml-1 (-0.59, -0.09); P < 0.05). A long-term reduction in maternal plasma AII, and an increase in fetal plasma renin concentration, were associated with 1 week of captopril administration. Neither drug had any consistent effect on plasma ACTH or cortisol concentrations in the pregnant ewe or fetus. These findings show that, during ovine pregnancy, antagonism of maternal AII activity, either by blockade of the AT1 receptor or by inhibition of AII synthesis, induces changes in the circulating components of the RAS in the mother and fetus. In both the pregnant ewe and fetus, the RAS is shown to be activated by suppression of AII activity.

Angiotensin II↗