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Biomedical subjects

J M Connell

Publications and source records attributed to J M Connell.

At least 163 records · Page 9Linked to original sources
PubMed1987

Does dopamine regulate aldosterone secretion in the rat?

This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH). Adrenal concentrations (means +/- SE) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 +/- 335, 527 +/- 75 and 51 +/- 12 nmol/g in the medulla, and 66 +/- 17, 18 +/- 9 and 6 +/- 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were greater than 3030.4, 339.8 +/- 41.5 and 55.2 +/- 11.0 pmol/l in rats fed low, normal and high sodium diets respectively. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1987

Duration of antithyroid action of methimazole estimated with an intravenous perchlorate discharge test.

We have used a method based on a perchlorate discharge test to estimate the duration of antithyroid effect of two doses of methimazole (MMI). Six patients with diffuse toxic goitre took 5 mg MMI twice daily and six took 20 mg twice daily over the study period of 12 weeks. Biochemical control of hyperthyroidism was achieved in all patients and thyroid hormone supplementation was required by all of the patients in the higher dose group to avoid hypothyroidism. Discharge of radioiodine from the thyroid by perchlorate diminished in both groups with time after MMI. After 5 mg MMI, perchlorate discharge as a percentage of the 30-min uptake (mean +/- SD), was 81.7 +/- 3.3% at 2.2 h, 69.3 +/- 18.9% at 5.9 h, 22.6-23.4% at 13.4 h and 2.7-6.7% at 25.1 h. After 20 mg MMI, the discharge was 92.5 +/- 1.9% at 2.2 h, 84.3 +/- 8.8% at 6.3 h, 64.8 +/- 24.1% at 13.3 h and 26.9-29.4% at 25.1 h. Only four patients (one in the lower dose group) showed a detectable discharge at 25 h and one of the patients treated with the lower dose showed no discharge at 13 h. These estimates of the effect of MMI on thyroidal iodide organification are not in keeping with published thyroidal MMI concentrations which do not show a fall between 3-6 h and 17-20 h after carbimazole. The explanation for this disparity is not clear but may be based on a redistribution of thioureylenes within the thyroid with time after dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Neuropeptide Y in multiple endocrine neoplasia: release during surgery for phaeochromocytoma.

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.

Adrenal Gland Neoplasms↗
PubMed1987

Effect of sodium depletion on pressor responsiveness in ACTH-induced hypertension in man.

1. Pressor responsiveness to angiotensin II (AII) and phenylephrine (PHE) was measured before and after 5 days of ACTH (1 mg i.m. daily) in six normal men maintained on low sodium diet (15 mmol daily). 2. ACTH caused a significant increase in systolic blood pressure of 9 mmHg. 3. There was no change in pressor responsiveness to AII with ACTH. 4. ACTH increased pressor responsiveness to PHE for both systolic and diastolic blood pressure, with a fall in the threshold for response from 0.9 to 0.6 micrograms/kg per min. 5. Increased pressor sensitivity to catecholamines during ACTH administration in man is not sodium-dependent.

Adrenocorticotropic Hormone↗
PubMed1987

Dopamine affects angiotensin II-induced steroidogenesis by altering clearance of the peptide in man.

Infusion of dopamine is reported to reduce the response of aldosterone to infused angiotensin II in sodium-deplete but not sodium-replete man. Six normal male subjects were infused with angiotensin II in graded doses (2, 4 and 8 ng/kg per min) with or without dopamine (1.0 microgram/kg per min) during both dietary sodium repletion and depletion. The responses of both aldosterone and 18-hydroxycorticosterone to infusion of angiotensin II appeared to be reduced by dopamine in sodium-deplete, but not sodium-replete, subjects. However, when the relationships between plasma concentrations of angiotensin II and corticosteroid were examined it was evident that plasma concentrations of angiotensin II were lower when dopamine was infused concurrently with the peptide (P less than 0.05). In a second study, six sodium-deplete males were infused with angiotensin II at a constant rate (6 ng/kg per min) while dopamine (or placebo) was given in graded doses (0.5, 1 and 5 micrograms/kg per min). Renal plasma flow was estimated from total body clearance of para-aminohippuric acid. Overall, angiotensin II concentrations were lower during dopamine infusion compared with those during infusion of placebo (63.2 +/- 9.7 (S.E.M.) vs 92.3 +/- 6.4 pmol/l; P less than 0.01) and this was associated with a 40% increase in effective renal plasma flow (627 +/- 68 vs 451 +/- 15 ml/min; P less than 0.05); there again appeared to be a reduced aldosterone response during combined angiotensin II/dopamine infusion compared with that during infusion of angiotensin II alone (1003 +/- 404 vs 1225 +/- 146 pmol/l; 0.05 less than P less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

18-Hydroxycorticosterone↗
PubMed1987

Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal man.

Both Adrenocorticotrophin (ACTH) and glucocorticoids raise blood pressure in man and animals, but the relationship of this and altered renal function to other cardiovascular variables, and the differences and similarities of the effects of the two agonists have not been fully explained. The present study compares the effects of ACTH (0.5 mg i.m; every 12 h) and cortisol (50 mg orally, every 6 h) in six normal men over a period of 5 days, preceded and followed by control periods of 3 and 2 days, respectively. Plasma cortisol levels were higher during ACTH treatment than during cortisol treatment. Both treatments raised blood pressure significantly and caused a marked antinatriuresis and expansion of extracellular fluid and plasma volume. ACTH also enhanced potassium excretion but this was less obvious for cortisol. Plasma concentrations of atrial natriuretic peptide rose to more than twice the basal level with both treatments. Both treatments markedly altered renal function. They raised glomerular filtration rate (GFR), i.e. inulin clearance (141% with ACTH; 113% with cortisol) although creatinine clearance was not changed, showing this to be an unreliable index during steroid administration. Filtration fraction (FF) also increased during both treatments, and renal blood flow (RBF) fell, although this achieved statistical significance only during cortisol treatment. Effective renal plasma flow [para-amino hippurate (PAH) clearance] remained unchanged while calculated renal vascular resistance increased. Fractional sodium reabsorption also rose but achieved statistical significance only during ACTH treatment. The similarity of response to treatment suggests that cortisol is largely responsible for the effects of ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1986

Reduced number of angiotensin II receptors on platelets in insulin-dependent diabetes.

Angiotensin II receptors on platelets were studied in 13 patients with uncomplicated type I diabetes mellitus and in 15 age-matched normal subjects. Receptor density on cells from the diabetic patients was 15% lower than the normal subjects (5.2 +/- 0.8 SD sites/platelet in diabetic patients and 6.4 +/- 0.8 in normals, P less than 0.001), but there were no differences in receptor affinity as measured by Kd (4.9 +/- 1.5 X 10(-10) mol/l in diabetic patients and 5.4 +/- 1.4 X 10(-10) mol/l in normals). Plasma concentrations of renin and angiotensin II were similar in both groups. The reduced density of angiotensin II receptors on platelets from patients with insulin-dependent diabetes may reflect a generalized abnormality of angiotensin II receptor regulation.

Adult↗
PubMed1986

Effect of low-dose dopamine infusion on insulin and glucagon release in fasting normal man.

The effect of a low-dose infusion of dopamine on basal circulating concentrations of insulin, glucagon and glucose in six healthy male subjects is reported. Dopamine (0.1 microgram/kg/min) or placebo was given intravenously for 60 minutes. During infusion of the catecholamine, circulating plasma dopamine was 3.46 +/- 1 ng/ml. No change in circulating concentrations of insulin, glucagon and glucose were seen during infusion of dopamine when compared with placebo infusion. It is concluded that dopamine acting at a D2 receptor is unlikely to be of physiological importance in regulation of basal pancreatic islet cell function in man.

Blood Glucose↗
PubMed1986

Dopamine effects on 11-deoxycorticosterone concentrations in patients with Cushing's syndrome and in vitro.

The effect of dopamine (1 micrograms/kg/min by i.v. infusion) on corticosteroid levels was studied in five patients with cortisol excess caused by increased ACTH secretion. In four of the five subjects dopamine, when compared with placebo infusion, caused plasma concentrations of 11-deoxycorticosterone to rise without affecting levels of cortisol, corticosterone or aldosterone. In a parallel in-vitro study using incubations of bovine adrenal zona glomerulosa cells, dopamine (10(-9) mol/l-10(-5) mol/l) had no effect on basal or ACTH stimulated secretion of aldosterone, cortisol or 11-deoxycorticosterone. However, dopamine (10(-5) mol/l) partially inhibited angiotensin II (10(-7) mol/l) stimulated secretion of aldosterone (4.36 ng/10(6) cells/h +/- 0.28 vs 2.90 +/- 0.20, P less than 0.05) but did not alter 11-deoxycorticosterone secretion i the same incubations. these data suggest that the effect of dopamine on 11-deoxycorticosterone secretion in vivo may not be due to its direct action on the adrenal to inhibit corticosteroidogenesis. An alternative explanation is that dopamine may alter extra-adrenal synthesis of 11-deoxycorticosterone, possibly by increasing substrate availability to tissues capable of 21-hydroxylation reactions.

Adrenal Cortex↗
PubMed1986

Pressor responsiveness in steroid-induced hypertension in man.

Pressor responsiveness to angiotensin II (AII) and phenylephrine (PE) was examined before and after 5 days of ACTH (1 mg, i.m., daily) or hydrocortisone (200 mg, orally, daily) in six normotensive men. Pulse pressure was higher prior to PE than AII infusion, presumably due to feeding. Systolic blood pressure (SBP) was increased by both ACTH and hydrocortisone treatment, but more by ACTH. There were no significant changes in AII pressor responsiveness with either ACTH or hydrocortisone. ACTH increased pressor responsiveness to PE at 1.35 and 2 micrograms/kg per min, and hydrocortisone at 0.6-2 micrograms/kg per min, with falls in pulse rate at 0.3-0.9 micrograms/kg per min. Changes in pressor responsiveness do not explain ACTH hypertension.

Adrenocorticotropic Hormone↗
PubMed1986

Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis.

Isolated bovine adrenocortical cells were incubated with and without 3 ng/ml ACTH, with various concentrations (10-1000 micrograms/ml) of either cimetidine or ranitidine. Cortisol, corticosterone, and deoxycorticosterone outputs were measured. Cimetidine and ranitidine at 320 and 1000 micrograms/ml inhibited ACTH-stimulated corticosterone and cortisol synthesis and cimetidine decreased basal cortisol synthesis. The inhibitory effects of cimetidine on cortisol synthesis were approximately 10 times greater than those of ranitidine. Cimetidine (1000 micrograms/ml), but not ranitidine increased deoxycorticosterone synthesis by ACTH-stimulated cells, indicating inhibition of 11 beta-hydroxylation in the adrenal steroidogenic pathway. Although doses of cimetidine and ranitidine which produce these in vitro effects are much greater than plasma concentrations in normal clinical use, they might be important in acutely ill patients given intravenous bolus injections of cimetidine, or if either antagonist were accumulated by the adrenal to produce high intracellular concentrations.

Adrenal Cortex↗
PubMed1986

Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?

Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p less than 0.01). Neither administration of dopamine (1 microgram/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1986

Dopamine effects on adrenocorticotrophin-stimulated aldosterone, cortisol, corticosterone and 11-deoxycorticosteroid concentrations in sodium-replete and sodium-deplete man.

The effect of dopamine (1 microgram/kg per min) on corticosteroid response to ACTH (0.1, 1 and 10 ng/kg per min) was compared with that of a placebo in sodium-replete (150 mmol/day) and -deplete (10 mmol/day) normal man. Dopamine had no effect on aldosterone, cortisol or corticosterone responses in either dietary phase, but increased deoxycorticosterone (897.0 +/- 126.4 (S.E.M.) vs 590.0 +/- 84.3 pmol/l, normal Na+; 1264.2 +/- 84.3 vs 764.5 +/- 84.3 pmol/l, low Na+) and deoxycortisol (6.033 +/- 0.583 vs 5.048 +/- 0.680 nmol/l, normal Na+; 5.112 +/- 0.600 vs 4.130 +/- 0.367 nmol/l, low Na+) levels during ACTH administration (all P less than 0.01). Deoxycorticosterone and corticosterone responses to ACTH were greater during sodium depletion than repletion (both P less than 0.01). Dopamine therefore increased 11-deoxycorticosteroid concentrations during ACTH-stimulated steroidogenesis. This may reflect action of dopamine to increase extra-adrenal formation of 11-deoxycorticosteroids.

Adrenal Cortex Hormones↗
PubMed1985

The role of plasma osmolality, angiotensin II and dopamine in vasopressin release in man.

A sensitive and specific radioimmunoassay for arginine vasopressin was used to compare the relative importance of changes in plasma osmolality, angiotensin II and dopamine in the regulation of vasopressin secretion in man. One hour after water loading plasma vasopressin fell from 0.40 to 0.06 pmol/l, while 8 h and 24 h fluid restriction resulted in a rise of vasopressin from 0.29 to 0.54 and 1.37 pmol/l respectively. In contrast neither dietary sodium deprivation, when plasma angiotensin II increased 5-fold, nor dopamine infusion, at a rate which increased circulating dopamine levels up to 244-fold, had any effect on basal plasma vasopressin values. These results confirm that, under physiological conditions, osmoregulation is the major mechanism controlling vasopressin release and suggests that circulating angiotensin II and dopamine have no significant part to play.

Adult↗
PubMed1985

Effect of low-dose dopamine infusion on basal and stimulated TSH and prolactin concentrations in man.

Dopamine (DA) infused at pharmacological doses in man inhibits thyrotrophin (TSH) secretion, although the physiological significance of this observation is unclear. The effect of low-dose DA infusion (0.1 microgram/kg/min) on TSH and prolactin (PRL) concentrations during stimulation with thyrotrophin releasing hormone (TRH) in normal male subjects is reported. Six subjects were given intravenous DA or placebo infusions for 165 min on separate days. A bolus of TRH (7.5 micrograms) was given at + 90 min, followed by infusion of the tripeptide (750 ng/min) for 45 min during both DA and placebo studies. In all subjects TRH administration caused a small rise in TSH which was partially inhibited by DA (peak 5.73 +/- 0.85 mU/l vs 4.58 +/- 1.09, P less than 0.05). PRL response to TRH was almost totally inhibited by DA (620 +/- 164 mU/l vs 234 +/- 96, P less than 0.05); integrated TSH and PRL responses to TRH were similarly inhibited by DA. Circulating plasma DA concentration during infusion of the catecholamine was 3.46 +/- 1.00 ng/ml, which is within the range reported in pituitary stalk plasma of other species. These data support the hypothesis that DA is a physiological modulator of TSH secretion in normal man. Major differences in the time course of TSH and PRL responses to TRH, and in the suppressive effect of DA on these responses suggest that there are fundamental differences in stimulus-secretion coupling for TRH and the lactotroph and thyrotroph.

Adult↗
PubMed1985

Kinetics of [123I]iodide uptake and discharge by perchlorate in studies of inhibition of iodide binding by antithyroid drugs.

Thyroidal binding of iodide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5-7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min-1 (normal greater than 0.15 min-1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min-1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min-1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12-14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.

Antithyroid Agents↗