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Biomedical subjects

D S Hart

Publications and source records attributed to D S Hart.

At least 19 recordsLinked to original sources
PubMed1983

Lack of direct effect of dopamine on aldosterone secretion in vivo.

Previous work suggests that aldosterone is modulated by dopamine, which exerts an inhibitory effect at the level of the adrenal cortex. This study reports the effect of dopamine on aldosterone secretion in conscious sheep with cervical adrenal transplants in whom endogenous ACTH secretion was suppressed by dexamethasone. In control experiments (n = 7) local adrenal infusions of angiotensin II (AII) (1.6 ng/min for 120 min) increased aldosterone secretion to peak levels (47.8 +/- 6.8 ng/min. mean +/- SEM) at 20 min, after which secretion fell to stable levels (20-28 ng/min) at 60-120 min. On separate days, sheep were restudied (n = 5) during systemic dopamine infusions (4 microgram/kg . min for 90 min), commencing 30 min before AII stimulation. There was no significant difference, either in the pattern or the sensitivity of the aldosterone response to AII, with dopamine infusions. Large intraadrenal infusions of dopamine (10 microgram/min) also failed to alter the aldosterone response to AII. The possibility that aldosterone was already under maximum tonic inhibition by dopamine was studied in four additional experiments using the dopamine blocking drug, metoclopramide. Although the systemic (iv) administration of metoclopramide increased aldosterone in both intact and transplanted sheep, local infusions of metoclopramide (0.5-15 microgram/min intraarterially) had no consistent effect on the aldosterone response to AII, and the addition of dopamine during metoclopramide infusions also had no effect. These results indicate that local (adrenal) dopaminergic mechanisms play little or no part in the regulation of aldosterone secretion in the sheep. The mechanism whereby aldosterone secretion is increased by systemic metoclopramide remains to be explained.

Adrenal Glands↗
PubMed1979

Long-term hormonal secretion from the autotransplanted sheep pancreas.

Seventy-five duct-ligated pancreatic segmental autotransplants were made into bipedicled skin loops on the necks of merino ewes by vascular suture to the carotid artery and jugular vein; the in situ pancreatic remnants apparently continued to function normally. Thirty-seven were found to be active hormone secretors (secretion-rate responses to Na butyrate greater than 1 mU/min for insulin or 5 ng/min for glucagon) when first tested approximately 1 month after transplantation; 12 remained active at 1 year, 5 at 2 years, and 4 at 3 years. At first testing, the responses were (mean +/- standard errors): insulin, 12.3 +/- 2.52 mU/min; glucagon, 52.6 +/- 13.5 ng/min. It is concluded that this autotransplant can, on occasion, be relatively long-lived and that it is a useful model with which to study not only pancreatic physiology but also non-immunological factors involved in survival of endocrine function in pancreatic transplants.

Animals↗
PubMed1979

Effect of ACTH on the aldosterone response to potassium in sheep with adrenal transplants.

The importance of physiological ACTH stimulation in maintaining the response of aldosterone secretion to potassium was studied in 5 conscious sheep with cervical adrenal autotransplants. Endogenous ACTH secretion was suppressed by dexamethasone. Constant local infusions of potassium that raised adrenal venous plasma by 2 mmol/l increased aldosterone secretion from 3 +/- 1 ng/min (mean +/- SE) to levels of 50 +/- 13 ng/min at 30 min, after which secretion fell to 14 +/- 6 ng/min at 230 min. Addition of submaximal ACTH (0.04 - 0.10 mU/min) to potassium infusions produced similar responses at 0--130 min, but aldosterone secretion increased at 130--190 min and was more sustained (40 +/- 9 ng/min at 230 min; P less than 0.05). Infusions of submaximal ACTH alone did not significantly increase aldosterone secretion above basal levels. Infusions of maximal ACTH (16.6 mU/min) produced higher aldosterone secretion in the group given ACTH replacement. These results show that the aldosterone response to potassium is phasic and poorly sustained in the absence of ACTH. Responsiveness can be restored by doses of ACTH insufficient alone to stimulate aldosterone secretion.

Adrenal Cortex↗
PubMed1978

Amino acid uptake by the mammary gland of the lactating ewe.

(1) The arterio-venous difference technique, previously used to measure mammary substrate uptake with cows and goats, was used to measure amino acid uptake by the mammary gland of the lactating Merino ewe. Possession of a single large superficial epigastric vein by the Merino ewe makes the Merino breed the most suitable for this type of study. (2) A method was developed enabling hourly measurement of milk yield without causing undue stress. Milk yield was essentially constant over a 7-8 h period. (3) Mammary extraction of most non-essential amino acids was low relative to output in milk protein and showed a greater variability with time than that found for the essential amino acids. There was a significant mammary extraction of ornithine and citrulline, neither amino acid being found in ovine milk protein. (4) Of the essential amino acids valine, isoleucine, leucine and arginine were taken up in excess of their requirement for milk protein synthesis. (5) On the basis of the extent of mammary extraction, methionine, lysine and leucine were first-, second- and third-limiting to the rate of milk protein synthesis. (6) Despite fluctuations in arterial amino acid concentrations the arterio-venous differences of the essential amino acids were relatively constant over a 7-8 h period. (7) The pattern of mammary amino acid uptake in the ewe is contrasted with that found in similar studies carried out with the lactating cow and goat.

Amino Acids↗
PubMed1978

Adrenocortical metabolism of angiotensin in sheep with adrenal transplants.

Conscious trained sheep with adrenal gland autotransplants in cervical skin loops were used to study adrenocortical metabolism and clearance of angiotensin (AII) administered by constant systemic infusion. For comparative purposes similar experiments were undertaken in five control sheep with skin loops but no cervical adrenal tissue. During AII infusions (0.33 microgram/min for 30 min), loop venous-arterial AII ratios (0.42--0.62 were similar in both groups of sheep. Measured AII clearances across the skin loop in sheep with and without adrenal transplants were 400--600 and 100--150 pg/min, respectively, which correlated with blood flow (r = 0.79), but showed no relation to aldosterone secretion rate. Analysis of AII immunoreactive fragments showed similar proportions of octa-, hepta-, and hexapeptide fractions (64, 26, and 5%, respectively) in adrenal arterial, adrenal venous, and systemic venous plasma. These studies do not support selective heptapeptide uptake or metabolism by adrenal tissue in vivo and indicate that specific adrenal binding of AII is likely to be less than 400 pg/min at arterial AII concentrations approximating 120 pg/ml.

Adrenal Cortex↗
PubMed1978

Failure of angiotensin II to inhibit corticotropin-stimulated cortisol secretion.

In view of the reported inhibitory effect of angiotensin II on cortisol secretion in human subjects, the effect of local angiotensin infusions on steroid secretion maintained by ACTH was examined by using sheep with cervical autotransplanted adrenal glands. During sustained submaximal stimulation by exogenous ACTH (40--80 microunit/min), the addition of local infusions of angiotensin II (1.6--160.0 ng/min) caused increased aldosterone and smaller increments in cortisol secretion in most experients. There was no evidence of inhibition of cortisol secretion by angiotensin. When similar experiments were undertaken during maximum stimulation by ACTH (16.6 mU/min), increments in aldosterone, but not in cortisol secretion, were observed. These studies exclude an acute inhibitory effect of angiotensin on cortisol biosynthesis, at least in ovine adrenal glands, during stimulation by ACTH.

Adrenal Glands↗
PubMed1976

Studies with the autotransplanted ovine pancreas: glucagon and insulin secretion.

Basic studies on the secretion of glucagon and insulin by the ovine pancreatic autotransplant in the neck are described. Of the 17 transplants in the series none failed to secrete glucagon and only three failed to secrete insulin in detectable amounts. The longest surviving transplant actively secreted both hormones 3 years after transplantation and five other transplants were functional and the animals healthy after 16 months. Exocrine secretion disappears shortly after transplantation. Sodium butyrate and alanine each promoted the secretion of both hormones by the transplant. Glucagon failed to promote insulin secretion by the transplant, although it apparently stimulated the ovine in situ pancreas. The immediate (presumably direct) effect of insulin was to inhibit transplant glucagon secretion. Hypoglycaemia induced by peripheral insulin administration failed to stimulate glucagon secretion by the transplant, although it did promote glucagon secretion by the ovine in situ pancreas. Heparin did not markedly suppress basal transplant secretion of either glucagon or insulin. Phasic response patterns occurred with both hormones during long butyrate perfusions, although first-phase responsiveness was not a constant feature. In one trial, first-phase responses fell off with repeated short butyrate infusions. Glucagon and insulin secretory patterns in response to butyrate were remarkably alike, suggesting a common mechanism. Loss of specific functions by the ovine pancreas after transplantation is discussed.

Animals↗