Biomedical subjects

A J Forhead

Publications and source records attributed to A J Forhead.

43 records · Page 3Linked to original sources

PubMed1996

Comparison of angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition in pregnant sheep during late gestation.

1. The effects of antagonism of the maternal renin-angiotensin system (RAS) with either an angiotensin II type 1-(AT1) specific receptor blocker (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) were compared in chronically-catheterised ewes and their foetuses during late gestation. 2. Daily from 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received i.v. either GR138950 (3 mg kg-1; n = 10), captopril (3 mg kg-1; n = 6) or an equivalent volume of vehicle solution (0.9% w/v saline; n = 10). 3. Within 2 h of drug administration, GR138950 abolished the maternal, but not the foetal, pressor responses to angiotensin II (AII; 100-188 ng kg-1, i.v.; P < 0.05), whereas captopril abolished both the maternal and foetal pressor responses to angiotensin I (AI; 400-750 ng kg-1, i.v.; P < 0.05). 4. On the first day of treatment, maternal blood pressure decreased in all GR138950-treated (-21 +/- 4 mmHg; P < 0.05) and captopril-treated (-13 +/- 5 mmHg; P > 0.05) ewes at 2 h after drug administration. Captopril also significantly decreased foetal blood pressure by 5 +/- 1 mmHg (P < 0.05). However, foetal blood pressure in the GR138950-treated animals remained unchanged. Maternal and foetal heart rates were unaffected by any treatment. Uterine blood flow was significantly reduced within 2 h of both GR138950 (-130 +/- 20 ml min-1; P < 0.05) and captopril (-72 +/- 16 ml min-1; P < 0.05) administration. 5. On the first day of treatment, maternal arterial haemoglobin (Hb) concentration and oxygen (O2) content increased at 2 h in all GR138950-treated and captopril-treated ewes. Foetal arterial pH and oxygenation (O2 content, O2 saturation and Pao2) were reduced by a similar extent in both groups of drug-treated ewes. 6. After one week of daily GR138950 administration, maternal blood pressure decreased from a pretreatment value of 96 +/- 5 mmHg on day 1 to 79 +/- 2 mmHg by day 7 (P < 0.05). Captopril treatment had no long-term effect on maternal blood pressure. Although foetal blood pressure increased by 3 +/- 1 mmHg over a week of vehicle treatment (P < 0.05), no significant differences were observed between the long-term changes in foetal blood pressure in all three groups of animals. 7. There were no long-term effects of drug administration on maternal Hb concentration or oxygenation, or on the foetal haematological parameters. However, changes in maternal PaCo2 observed in the GR138950-treated (+1.4 +/- 0.5 mmHg; P < 0.05) and captopril-treated (+3.3 +/- 1.1 mmHg; P > 0.05) ewes were significantly different from those seen in the vehicle-treated animals (P < 0.05). 8. There were no apparent adverse effects of maternal GR138950 or captopril treatment on foetal viability. 9. The present study demonstrated that administration of either GR138950 or captopril to pregnant ewes effectively blocked the maternal RAS, and caused hypotension and a decrease in uterine blood flow. However, only captopril appeared to cross the placenta to influence directly the RAS of the sheep foetus. This suggests that the fall in foetal oxygenation observed after AT1-specific receptor blockade and ACE inhibition originates primarily from changes in the maternal and/or placental vasculature. Despite these changes, neither GR138950 nor captopril were detrimental to the outcome of pregnancy when foetal blood loss was kept to a minimum.

Angiotensin Receptor Antagonists↗

PubMed1996

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

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 adrenalectomized 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.

Adrenalectomy↗

PubMed1995

Transport-induced stress responses in fed and fasted donkeys.

Plasma endocrine and metabolic responses to transport for 30 minutes and four hours were investigated in six fed donkeys. In the unstressed animals there was a pulsatile secretion of cortisol at two-hour intervals, from minima of 51.4 +/- 17.6 nmol litre-1 to maxima of 160.0 +/- 11.0 nmol litre-1, but during transport this pulsatility was lost and the animals' stress response was characterised by steady high concentrations of 110 to 220 nmol litre-1. The cortisol concentration decreased after the journey and remained at a minimum until the restoration of pulsatile secretion 8.5 to 10.5 hours later. The transport-induced adrenocortical response did not produce any significant changes in the plasma concentrations of triglycerides, cholesterol, glucose, total protein, albumin, globulin or urea. The donkeys' responses to transport for four hours were also investigated after they had been deprived of food for one or three days. Food deprivation alone increased plasma cortisol and triglyceride concentrations, and decreased glucose and insulin concentrations, and transport consistently, and feeding after the journey sometimes, accentuated their adrenocortical function; the changes in cortisol concentrations as a result of the journey tended to be lower than in the fed animals. Transport had no effect upon the triglyceride response to either period of fasting. Hyperglycaemia was induced by transport in four of the six donkeys fasted for one day and in all of them after three days of fasting.

Analysis of Variance↗

PubMed1995

Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep.

An AT1-specific angiotensin II receptor antagonist (GR117289; 1 mg/kg I.V. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until parturition (139 +/- 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/- 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbilical blood flows measured by steady-state infusion of tritiated water were -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/min at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg), saturation (-6.6 +/- 1.6%) and content (-0.3 +/- 0.1 mumol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0.5-1 h following drug administration (P < 0.01; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289-treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle- and GR117289-treated groups of ewes with single fetuses.

Angiotensin Receptor Antagonists↗

PubMed1994

Relationship between plasma insulin and triglyceride concentrations in hypertriglyceridaemic donkeys.

Hyperinsulinaemia is a commonly-observed characteristic of insulin resistance, and a reduction in insulin sensitivity is thought to be either a causative and/or symptomatic feature of equine hyperlipaemia. A positive correlation (r = 0.545, P = 0.0015) existed between plasma insulin and triglyceride concentrations determined in 31 donkeys with naturally occurring hyperlipidaemia/hyperlipaemia. Greater insulin values tended to occur in the animals with an overweight body score. Inter-animal variation in insulin concentrations, however, prevented the identification of any differences either within hypertriglyceridaemic donkeys (when classified by clinical condition, date of arrival to a sanctuary and eventual outcome after treatment) or between groups of normotriglyceridaemic (n = 6) and experimentally fasted hypertriglyceridaemic (n = 5) donkeys. Determination of basal plasma insulin concentrations may not provide an accurate assessment of underlying insulin sensitivity. Alternatively, hyperinsulinaemia may be evident only in animals with established insulin resistance.

Animals↗

PubMed1994

Transport stress delays the oestradiol-induced LH surge by a non-opioidergic mechanism in the early postpartum ewe.

The present study was designed to investigate whether transport, a mild environmental stressor, could affect the oestradiol-induced LH surge in postpartum ewes and, if so, the mechanism involved. Welsh Mountain ewes, with lambs removed at parturition (day 0) and hand-milked 12 and 48 h later, were given 50 micrograms oestradiol benzoate intramuscularly at various times postpartum. Blood samples were taken via an indwelling jugular venous catheter every 2 h from 8 to 24 h after oestradiol injection. All results are given as means +/- S.D. On day 1 oestradiol was unable to induce an LH surge in any ewe. Transport (10-14 h after oestradiol) delayed the onset of the oestradiol-induced LH surge on day 14 (17.5 +/- 1.7 vs 14.4 +/- 2.0 h, n = 5 each; P < 0.05), but not on day 28 (14.9 +/- 2.0 vs 14.0 +/- 2.4 h, n = 5 out of 7). Transport had no effect on the amplitude of the surge on either day. Naloxone treatment (1 mg/kg per 2 h) was unable to prevent the delay caused by transport (18.0 +/- 1.1 vs 17.5 +/- 1.7 h, n = 8 each), and did not affect the amplitude of the surge (28.4 +/- 5.3 vs 28.1 +/- 2.3 ng/ml, n = 8 each).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Plasma glucose and cortisol responses to exogenous insulin in fasted donkeys.

Susceptibility to equine hyperlipaemia is increased by poor food intake. To assess the contribution of changes in insulin sensitivity, plasma glucose and cortisol responses to an intravenous insulin challenge (0.4 IU kg-1 bodyweight) were compared with those observed after saline administration in six donkeys fasted either overnight or for three days. Three days of fasting decreased both the rate of insulin-induced hypoglycemia and the maximal hypoglycemic response. A transitory increase in plasma cortisol which peaked within one to four hours of insulin administration was observed in three of the six overnight-fasted donkeys and in all of the three-day fasted donkeys; inter-animal variation appeared to exist in the responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulation by insulin-induced hypoglycemia. Fasting is likely to present a risk of equine hyperlipaemia, at least on part, by the reduction in tissue sensitivity to the glucoregulatory action of insulin.

Animals↗