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Biomedical subjects

M G Buckley

Publications and source records attributed to M G Buckley.

At least 73 records · Page 4Linked to original sources
PubMed1989

Raised plasma levels of atrial natriuretic peptides in Addison's disease.

Plasma levels of atrial natriuretic peptides (ANP) were significantly higher in 7 patients with treated Addison's disease (15.8 +/- 8.8 pg/ml, mean +/- SD) than in 7 control subjects (6.1 +/- 3.8 pg/ml) matched for sex, age, body weight and blood pressure. All subjects were studied on their usual sodium intake and had similar urinary sodium excretions. These findings indicate inappropriately high levels of plasma ANP in patients with treated Addison's disease and are possibly due to the lack of adrenal control on ANP synthesis and/or secretion in these patients.

Addison Disease↗
PubMed1989

Prolonged decrease in blood pressure after atrial natriuretic peptide infusion in essential hypertension: a new anti-pressor mechanism?

1. To study the anti-hypertensive effects of atrial natriuretic peptide (ANP), eight patients with mild to moderate essential hypertension, on no treatment, were infused with alpha-human ANP (102-126) (37 pmol min-1 kg-1) or placebo for 60 min and observed for a further 4 h on the fifth day of low and high sodium diets in a randomized, cross-over study. 2. Plasma ANP levels increased over 30-fold into the high pathophysiological range during ANP infusion, but had returned to control values by 60 min after the end of infusion. With ANP infusion, there was a large decrease in supine blood pressure which was similar on both the low and high sodium intakes and was maximal 20-40 min after completion of the infusion. These reductions in blood pressure were sustained for a further 4 h after the end of ANP infusion and for 3 h after plasma ANP levels had returned to control values. 3. Maximal urinary sodium excretion increased 10-fold on the low sodium diet (negative sodium balance 20 mmol) and threefold on the high sodium diet (negative sodium balance 30 mmol) during ANP infusion; however, during the 4 h after infusion, urinary sodium excretion was below placebo values. During ANP infusion, packed cell volume increased significantly on both diets but returned to control values by 4 h after the end of infusion. 4. There were no significant changes in plasma renin activity compared with placebo during or after ANP infusion. However, plasma aldosterone was significantly greater than placebo values after the end of ANP infusion on both low and high sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Immunoreactive N-terminal pro-atrial natriuretic peptide in human plasma: plasma levels and comparisons with alpha-human atrial natriuretic peptide in normal subjects, patients with essential hypertension, cardiac transplant and chronic renal failure.

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Atrial natriuretic peptides and tubular sodium handling during normal daily life in men.

The relationship between segmental renal tubular sodium handling (using the renal clearance of ingested lithium as a marker of proximal tubular sodium handling) and circulating plasma levels of atrial natriuretic factor (ANF) was studied in a sample of 295 untreated men drawn from a male population at work under their usual living conditions. Plasma ANF was positively and significantly related to sodium excretion at the distal nephron, indicating that this hormone interacts with a distal renal tubular site to influence the control of sodium excretion in man.

Adult↗
PubMed1989

Hormonal responses to gradual changes in dietary sodium intake in humans.

The effects of gradual (50 mmol/day) increases in dietary sodium intake from 10 to 350 mmol/day on plasma atrial natriuretic peptide (ANP), aldosterone, and plasma renin activity (PRA) were studied in six normal subjects. With the increases in sodium intake there was a progressive increase in urinary sodium from 12.2 +/- 4.4 to 314.8 +/- 31.4 mmol/24 h; plasma ANP increased gradually from 9.9 +/- 1.1 to 23.3 +/- 2.2 pg/ml, with the increases being closely associated with the changes in cumulative sodium balance. Plasma aldosterone decreased significantly from 2,519.7 +/- 147.4 pmol/l on the 10 mmol/day to 1,393.3 +/- 125.4 pmol/l when the sodium intake was increased to 50 mmol/day and decreased further to 251.6 +/- 78.7 pmol/l by the end of the study. The changes in PRA paralleled those in plasma aldosterone with the exception of no significant change in plasma PRA within 24 h of the initial increase in sodium intake. This marked sensitivity in the responses of both the ANP and the renin-aldosterone system to small increases in sodium intake clearly points to their importance in the renal adaptations to alterations in dietary sodium intake.

Adult↗
PubMed1989

Characteristics of the distribution of plasma atrial natriuretic peptides in a cross-sectional study of middle-aged untreated male workers.

The distribution of the plasma levels of atrial natriuretic peptide (ANP) and their statistical correlates were studied in a random sample of 306 untreated male workers in southern Italy. Plasma ANP was not normally distributed in the population sample, with values skewed to the right and significantly shifted from the normal Gaussian curve (p = 0.003). In a multivariate analysis, plasma ANP was independently and positively related to age (p less than 0.001), urinary sodium excretion (p less than 0.01), and inversely related to creatinine clearance (p less than 0.02).These variables explained more than 12% of the variability of plasma levels of ANP. These findings confirm, in a random sample of untreated male workers, the importance of age and renal function in predicting ANP levels in the plasma and emphasize the potential importance of ANP in the control of sodium excretion in humans under free living conditions.

Adult↗
PubMed1988

Endocrine and renal response to water loading and water restriction in normal man.

1. Nine normal subjects (eight male, one female) on a fixed daily intake of 150 mmol of sodium and 80 mmol of potassium, were randomized to receive either 3 days of 1.0 litre total water intake/24 h (food + fluid) or 4 days of 6.8 litres total water intake/24 h, and were then crossed over after a 3 day control period (2.7 litres water/24 h). 2. During water restriction, urine volume fell from 1.94 litres/24 h to less than 1 litre/24 h by the first day and was 0.77 litre/24 h on the final day. Plasma atrial natriuretic peptide levels were unchanged from baseline despite a large increase in plasma vasopressin and plasma and urine osmolality. Urinary sodium was unaltered throughout, while urinary potassium was increased on the final 2 days of water restriction. 3. During water loading, urine volume increased from 1.85 litres/24 h to 5.44 litres/24 h on the first day and remained at approximately 6 litres/24 h for the final 3 days. Plasma atrial natriuretic peptide showed no change. Plasma vasopressin and plasma and urine osmolality were reduced. Urinary sodium and potassium output were unchanged from baseline. 4. These results suggest that changes in plasma atrial natriuretic peptide are unlikely to be involved in the normal homoeostatic response to changes in water balance in man.

Adolescent↗
PubMed1988

Plasma atrial natriuretic peptide in essential hypertension. Comparison with normotensive subjects and effects of changes in dietary sodium intake.

Plasma levels of atrial natriuretic peptide (ANP) in 106 patients with essential hypertension with a supine mean blood pressure (mean +/- SEM) of 128.9 +/- 1.6 mmHg and not on treatment were significantly higher than those in 47 normotensive subjects (supine mean blood pressure 93.9 +/- 1.2 mmHg) with mean values of 17.2 +/- 1.1 and 8.6 +/- 0.6 pg/ml, respectively (P less than 0.001). Similar results were found in a subgroup of 35 hypertensive patients identically matched in terms of age, sex, and race with 35 normotensive subjects. Plasma levels of ANP were correlated significantly with age in normotensive subjects and with age and blood pressure in the hypertensive patients. In 12 hypertensive patients studied on a low (10 mmol sodium/day), on their usual sodium intake (around 120 mmol sodium/24 hr) and on a high (350 mmol sodium/day) intake, plasma ANP increased approximately twofold by the fifth day of the high sodium intake, but there was no significant difference between the plasma levels on their usual sodium intake and those on the fifth day of the low sodium intake. Supine mean blood pressure on the patients' usual sodium intake was 119.3 +/- 2.7 mmHg and was reduced to 110.0 +/- 3 mmHg by the fifth day of the low sodium intake (P less than 0.005). However, there was no significant difference between the blood pressure levels on their usual and high sodium intake (118.3 +/- 3.0 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Atrial natriuretic peptide in human plasma--comparison of radioreceptor versus radioimmunoassay.

A sensitive and specific procedure for the measurement of atrial natriuretic peptide (ANP) in human plasma by radioreceptor assay, using bovine adrenal membranes treated with Triton-X-100, is described. Plasma levels (mean +/- SEM) of ANP in healthy subjects on a normal sodium intake were 8.4 +/- 1.4 pg/ml and could be modified by changes in sodium intake with increases in sodium intake being associated with higher levels. Mean plasma ANP was approximately 2-fold higher in patients with essential hypertension and 4-fold higher in patients with cardiac or renal disease. The values obtained were comparable in magnitude to those obtained by radioimmunoassay and there was a strong correlation (r = 0.94; p less than 0.001) between the values obtained by radioimmuno- and radioreceptor-assay. These results suggest that circulating ANP corresponds to the biologically active peptide and point to an important role of the atrial peptides in the control of sodium balance.

Adult↗
PubMed1987

Regulation of fatty acid synthesis and malonyl-CoA content in mouse brown adipose tissue in response to cold-exposure, starvation or re-feeding.

1. The effect of nutritional status on fatty acid synthesis in brown adipose tissue was compared with the effect of cold-exposure. Fatty acid synthesis was measured in vivo by 3H2O incorporation into tissue lipids. The activities of acetyl-CoA carboxylase and fatty acid synthetase and the tissue concentrations of malonyl-CoA and citrate were assayed. 2. In brown adipose tissue of control mice, the tissue content of malonyl-CoA was 13 nmol/g wet wt., higher than values reported in other tissues. From the total tissue water content, the minimum possible concentration was estimated to be 30 microM 3. There were parallel changes in fatty acid synthesis, malonyl-CoA content and acetyl-CoA carboxylase activity in response to starvation and re-feeding. 4. There was no correlation between measured rates of fatty acid synthesis and malonyl-CoA content and acetyl-CoA carboxylase activity in acute cold-exposure. The results suggest there is simultaneous fatty acid synthesis and oxidation in brown adipose tissue of cold-exposed mice. This is probably effected not by decreases in the malonyl-CoA content, but by increases in the concentration of free long-chain fatty acyl-CoA or enhanced peroxisomal oxidation, allowing shorter-chain fatty acids to enter the mitochondria independent of carnitine acyltransferase (overt form) activity.

Acetyl Coenzyme A↗
PubMed1987

Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man.

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5 +/- SEM 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 +/- 2.4 pg/ml) to day 7 (15.1 +/- 2.6 pg/ml). The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium 'escape' occurred by days 4 to 7. These results support the concept that ANP could play an important hormonal role in over-coming the sodium-retaining effects of mineralocorticoids in man.

Adult↗
PubMed1987

Dissociation between plasma atrial natriuretic peptide levels and urinary sodium excretion after intravenous saline infusion in normal man.

1. Plasma immunoreactive atrial natriuretic peptide (ANP) and urinary sodium excretion were measured in six normal male subjects before, during and for 195 min after a 60 min infusion of 2 litres of saline (0.9% NaCl, 308 mmol of Na+). 2. During the saline infusion, there was a significant increase in plasma ANP and urinary sodium excretion and a significant decrease in plasma renin activity, aldosterone, albumin, creatinine and packed cell volume. 3. The maximal rise in mean plasma ANP occurred 15 min after stopping the infusion and the maximal rise in mean urinary sodium excretion in the collection period 30 min later. 4. Plasma ANP then decreased so that by the end of the study the level was the same as before the saline infusion. However, at this time, 195 min after the saline infusion was stopped, there was still a net positive sodium balance of 220 mmol and urinary sodium excretion remained significantly elevated. 5. Our results are compatible with the concept that increased ANP secretion may play a role in the immediate increase in sodium excretion after a saline load. However, they also suggest that other mechanisms may be more important for the longer term increase in sodium excretion.

Adult↗
PubMed1987

Secretion of atrial natriuretic peptide from the heart in man.

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.

Aged↗
PubMed1986

Raised concentrations of plasma atrial natriuretic peptides in cardiac transplant recipients.

Plasma atrial natriuretic peptide concentrations were measured by radioimmunoassay six to 77 weeks after operation in eight cardiac transplant recipients with no appreciable evidence of cardiac failure or rejection and in eight control subjects matched for age, sex, race, and blood pressure. Plasma atrial natriuretic peptide concentrations were significantly higher in the cardiac transplant recipients (mean 19.4 (SE 3.9) ng/l) than in the controls (7.3 (1.2) ng/l p less than 0.01). The mechanisms underlying these raised values were not clear. These findings suggest that the transplanted atria may secrete atrial peptides and also that innervation is not obligatory for secretion of atrial natriuretic peptides to occur. Before this can be confirmed, however, it remains to be established what the relative contribution of donor and recipient atrial tissue is to the secretion of these peptides.

Adult↗
PubMedDate not supplied

Effects of interleukin-4 or stem cell factor on mast cell mediator release and cytokine gene expression.

We have investigated the capacity of interleukin (IL)-4 or stem cell factor (SCF) to induce direct mediator release from rodent peritoneal mast cells, and also to induce or regulate cytokine gene expression in the human HMC-1 mast cell line. SCF, but not IL-4, induced low levels of serotonin release from mouse or rat peritoneal mast cells; rat mast cells acquired enhanced responsiveness to SCF during culture. IL-4, but not SCF, enhanced ionomycin-induced transcription and secretion of several genes, including the cytokines IL-3, IL-4, granulocyte/macrophage-colony-stimulating factor, IL-8 and the receptor for IL-6 in the human HMC-1 mast cell line.

Animals↗