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Biomedical subjects

A M Cumming

Publications and source records attributed to A M Cumming.

At least 55 records · Page 3Linked to original sources
PubMed1984

Metabolic effects of high dose amiloride and spironolactone: a comparative study in normal subjects.

Amiloride (75 mg daily) and spironolactone (300 mg daily) were given to five normal subjects for 7 days in order to compare metabolic effects at maximal doses. Blood pressure, body weight, Na+ and K+ balance, and plasma concentrations of Na+, K+, active and total renin, angiotensin II, aldosterone, 11-deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OH DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH B) and cortisol were measured before and on each day of treatment. Natriuresis and K+ retention were significantly greater with amiloride. Plasma K+ increased from 4.1 +/- 0.2 to 4.9 +/- 0.2 mmol/l (mean +/- s.d.) on amiloride and from 4.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l with spironolactone. Stimulation of renin, angiotensin II, aldosterone and 18-OH B occurred with both drugs but was greater with amiloride in each case. A transient decrease in systolic and diastolic blood pressure was observed after 2 days of spironolactone treatment but not with amiloride. The slope of the regression of aldosterone on angiotensin II during spironolactone treatment was less than that with amiloride, consistent with partial blockade of aldosterone synthesis by spironolactone. These data suggest that the maximum metabolic effects of amiloride exceed those of spironolactone.

Adult↗
PubMed1984

Polymorphism at the apoprotein-E locus in relation to risk of coronary disease.

The frequency of genotypes at the polymorphic locus which codes for Apoprotein-E, an important constituent of very low density serum lipoprotein, has been determined in a random sample of persons between the ages of 45 and 60 years, born in the Grampian Region of North East Scotland. Three alleles, EII, EIII and EIV occur with a frequency of respectively 0.08, 0.77 and 0.15. In a random sample of survivors of myocardial infarction, born in the same region, genotype EIVEIII occurs more and EIIIEII less frequently than expected. Also the mean age at first infarction is lower in men for genotype EIVEIII than for other genotypes. Commonly occurring genotypes at this locus apparently influence the risk of coronary disease. A prospective study is needed to show how the genetic effects are expressed.

Age Factors↗
PubMed1984

A search for the mechanism underlying the altered MCV in thyroid dysfunction: a study of serum and red cell membrane lipids.

The mean red cell volume (MCV) is increased in hypo- and decreased in hyperthyroidism but the underlying cause(s) is unknown. In view of the well recognised alterations in serum lipids in thyroid dysfunction, we have examined the possibility that a corresponding alteration in the amount or distribution of lipids in the red cell membrane may account for the red cell volume changes. Our findings however do not support this hypothesis.

Adult↗
PubMed1984

The gene for apolipoprotein C-II is closely linked to the gene for apolipo-protein E on chromosome 19.

We have used a common TaqI restriction fragment length polymorphism (RFLP) near the human apolipoprotein C-II (apoC-II) gene to study linkage with apolipoprotein E (apoE). The inheritance of the apoC-II RFLP was followed in seven families that were segregating for apoE protein variants. No recombinants were observed in 20 informative meioses, giving an overall lod score of greater than 4.0 at recombination fraction 0. We have also observed apparent linkage disequilibrium between apoE and the apoC-II RFLP. Taken together these results demonstrate that these two apolipoprotein genes are closely linked and confirm that the gene for apoC-II is on human chromosome 19.

Apolipoprotein C-II↗
PubMed1984

Enalapril in hypertension with renal artery stenosis: long-term follow-up and effects on renal function.

Enalapril alone, 10-40 mg given once-daily, controlled systemic hypertension long-term (mean follow-up time 19 months) in patients with renal artery stenosis. Significant, but usually modest, increases in serum creatinine and urea were observed. No serious side-effects were seen. A highly significant reduction in peripheral plasma angiotensin II was maintained 24 h after the previous dose of enalapril. Plasma active renin concentration rose 20-fold with long-term enalapril, when the stenotic kidney showed significant secretion of inactive, as well as of active renin. With enalapril therapy, the contralateral kidney showed net extraction of active renin. In unilateral renal artery stenosis, circulation on the affected side is diminished and is mainly via the juxtamedullary nephrons, which become rich in associated renin. Important intrarenal compensatory actions of the renin-angiotensin system include support of glomerular filtration, enhancement of vasa recta-mediated counter-current exchange, sustained urea excretion and maintenance of renal artery pressure distal to the stenosis. These compensatory effects are lost with converting enzyme inhibition. Thus in patients who are candidates for operation, enalapril should usually be given for no more than one month before proceeding to corrective surgery, to allow maximum blood pressure reduction without endangering the stenotic kidney for too long. Enalapril can nevertheless be given effectively long-term in patients unsuitable for corrective surgery.

Adolescent↗
PubMed1984

Renal secretion of inactive renin and extraction of angiotensin II in renal artery stenosis in man: factors determining renal vein renin ratio.

Triplicate blood samples were obtained, without stimulation, simultaneously from the aorta and both renal veins in 24 untreated hypertensive patients with unilateral renal artery stenosis. Across the affected kidney the plasma concentrations of active renin, inactive renin and angiotensin II increased by 363% (P less than 0.001), 80% (P less than 0.05) and 100% (P less than 0.05) respectively. Thus the affected kidney was secreting both active and inactive renin, while appreciable quantities of angiotensin II were generated across the renal circulation on that side. Across the contralateral unaffected kidney there were no significant changes in concentration of active or inactive renin, indicating net suppression of secretion of both forms of renin. Plasma angiotensin II concentration was however markedly reduced, to 50% of the arterial value (P less than 0.001), in the contralateral renal vein, demonstrating renal extraction of angiotensin II. In 14 patients renal plasma flow was also measured. The ratio of active renin concentration between the two renal veins correlated more closely with the renal plasma flow to the affected kidney (r = -0.81; P less than 0.01) than with renin secretion rate on that side (r = +0.37; NS). Thus reduction in renal blood flow rather than increase in renin secretion appeared to be the major determinant of renal vein renin ratio.

Angiotensin II↗
PubMed1983

Enalapril in the treatment of hypertension with renal artery stenosis.

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in angiotensin I; this probably reflects the fall in renin substrate that occurs with converting enzyme inhibition. Enalapril alone caused reduction in exchangeable sodium, with distinct increases in serum potassium, creatinine, and urea. Enalapril was well tolerated and controlled hypertension effectively long term; only two of the 20 patients required concomitant diuretic treatment.

Adolescent↗
PubMed1983

Inverse relation of exchangeable sodium and blood pressure in hypertensive patients with renal artery stenosis.

Measurements of exchangeable sodium, arterial pressure and plasma concentrations of active renin, angiotensin II, aldosterone, sodium and potassium were made in 35 hypertensive patients with renal artery stenosis, 30 having unilateral renal arterial lesions. Plasma urea was below 7 mmol/l in 24 of the patients with unilateral lesions. In these and in the whole group of 35 patients there were significant inverse correlations between exchangeable sodium and diastolic blood pressure and between plasma sodium concentration and diastolic pressure. Six patients had hyponatraemia with a plasma sodium concentration less than 135 mmol/l. All were sodium-deplete with secondary hyperaldosteronism, three also having malignant-phase hypertension. Twelve of the patients with unilateral renal artery stenosis underwent bilateral ureteric catheterization. Sodium excretion was greater from the contralateral kidney than from the affected kidney and the rate of sodium excretion from the former, but not from the latter, was significantly related to arterial pressure. The relation of diastolic blood pressure and exchangeable sodium is the opposite of the positive correlation found in essential hypertension and Conn's syndrome. In renal artery stenosis the inverse correlation could result from a natriuretic effect of increased arterial pressure occurring mainly in the contralateral kidney.

Adult↗
PubMed1983

The renin-angiotensin system and total body sodium and potassium in hypertensive women taking oestrogen-progestagen oral contraceptives.

Measurements of total body sodium and potassium, and of components of the renin-angiotensin-aldosterone system, were made in a group of women who developed hypertension while taking oestrogen-progestagen oral contraceptives. The results were compared with similar measurements made in age-matched women with essential hypertension. Total body sodium and potassium were normal in both groups. Plasma renin-substrate was significantly elevated in the women taking oral contraceptives, while concentrations of active renin were similar and normal in both groups. Thus plasma angiotensin II was significantly elevated in the pill users; overall the product of renin and renin substrate concentrations correlated significantly with angiotensin II. The rise in plasma angiotensin II in conjunction with normal total body sodium could therefore contribute to the increase in blood pressure induced by oestrogen-progestagen oral contraceptives.

Adult↗
PubMed1983

Primary hyperparathyroidism associated with primary hyperaldosteronism.

Two patients with both primary hyperparathyroidism and primary hyperaldosteronism are described. Each presented with high blood pressure and a history of renal calculi. Mild hypercalcaemia was associated with raised plasma parathyroid hormone concentrations and a parathyroid adenoma was excised from each. Both patients also had hypokalaemia, hyperaldosteronism and low plasma renin concentrations. Quadric analysis, adrenal vein plasma aldosterone concentrations, adrenal venography and CT scanning all suggested an adrenal adenoma in each patient. This suspicion was confirmed at operation in one patient; the other patient is unfit for adrenal surgery but her blood pressure and plasma potassium concentration have remained within the normal range during prolonged treatment with either spironolactone or amiloride. Because of this unusual association a search was made for parathyroid hormone excess in patients with primary hyperaldosteronism and for aldosterone excess in primary hyperparathyroidism. None was found.

Adult↗
PubMed1983

Enalapril (MK421) in the treatment of hypertension with renal artery stenosis.

The converting enzyme inhibitor, enalapril, was given to 20 hypertensive patients with renal artery stenosis in a single daily dose of 10-40 mg. Enalapril effectively controlled hypertension long-term, and only two of the 20 patients required concomitant diuretic treatment. The blood pressure reduction 6 h after the first dose of enalapril was significantly related to pre-treatment plasma concentrations of active renin and angiotensin II (AII), and to the concurrent fall in AII. Blood pressure fell further with continued treatment; the long-term reduction was not significantly related to pretreatment plasma renin or angiotensin II. At three months, 24 h after the last dose of enalapril, blood pressure, plasma AII and converting enzyme activity remained low, and active renin and angiotensin I (AI) high; 6 h after dosing, AII had, however, fallen further. During prolonged therapy, the increase of active renin was proportionately greater than that of angiotensin I. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight increases in serum potassium, creatinine and urea. Enalapril alone did not impair overall renal function in five patients with bilateral renal lesions despite effective blood pressure reduction. Enalapril was well tolerated with no serious side-effects. Enalapril given once daily is effective in controlling hypertension associated with renal artery stenosis.

Adolescent↗
PubMed1983

The decision on surgery in renal artery stenosis.

Eighty-six hypertensive patients with arteriographic evidence of renal artery stenosis presented between 1968 and 1979. Thirty-nine subsequently underwent surgery and were followed thereafter for at least one year. In 54 per cent blood pressure was reduced to within one standard deviation of the mean for a normal individual of the same sex and age. A further thirty-one per cent of patients were 'improved', but needed hypotensive drugs to maintain blood pressure within this range. In the remaining 15 per cent of patients the operation did not reduce blood pressure. The purpose of the study was to assess our ability to predict this varies surgical outcome using clinical observations and special tests. The latter included measurement of plasma renin concentration in both peripheral vein and renal vein plasma, catheterization of both ureters and studies of the response of blood pressure to brief infusion of saralasin. No single observation or test, no combination of observations or tests and no discriminant function clearly separated patients in whom surgery would succeed from those in whom it would fail. Renal vein renin ratio was the best test; all patients with a ratio greater than 2.0 underwent successful surgery, but so too did some patients with a lower ratio. We also analysed the factors which had influenced our decision to undertake special investigations in 65 of the 86 patients and, having done these investigations, to recommend surgery in 39. No single factor seemed to have had overriding importance in making these decisions.

Adolescent↗
PubMed1982

Captopril in the management of hypertension with renal artery stenosis: its long-term effect as a predictor of surgical outcome.

Fifteen patients with hypertension and unilateral renal artery disease were treated with captopril alone; 10 came to operation and were later assessed postoperatively with no drug treatment. Captopril caused both immediate and sustained decreases in plasma angiotensin II and aldosterone, with increases in plasma active renin and blood angiotensin I concentrations. Decrements in systolic and diastolic pressure 2 hours after the first dose of captopril were closely correlated with the initial decreases in plasma angiotensin II. Blood pressure was decreased by long-term captopril therapy irrespective of whether plasma angiotensin II was abnormally high before treatment. The long-term response of both systolic and diastolic pressure correlated well with the response to surgery. By contrast, the blood pressure decrease 2 hours after the initial dose of captopril variously underestimated and overestimated the decrease during prolonged use of the drug and did not relate to surgical outcome. In patients who, before treatment, had secondary aldosteronism, hyponatremia, hypokalemia and sodium and potassium deficiency, captopril corrected these abnormalities. In the remaining patients, long-term captopril therapy did not alter exchangeable sodium, plasma sodium or total body potassium, although plasma potassium levels increased.

Adolescent↗
PubMed1982

Captopril in renovascular hypertension: long-term use in predicting surgical outcome.

The angiotensin converting-enzyme inhibitor captopril was used as long-term preoperative treatment in a series of hypertensive patients with unilateral renal arterial disease. There were immediate and sustained falls in plasma angiotensin II and aldosterone concentrations, with converse increases in circulating renin and angiotensin I. In patients with sodium and potassium deficiency and secondary aldosterone excess before treatment captopril corrected the sodium and potassium deficits; in these cases the initial hypotensive response was profound but the later effect was less pronounced. When sodium and potassium state was initially normal it remained unchanged during captopril treatment, while the full hypotensive effect took up to three weeks to be attained. The immediate, but not long-term, falls in arterial pressure with captopril were proportional to the immediate decrements of plasma angiotensin II. Nevertheless, while the immediate blood-pressure reduction with captopril variously overestimated and underestimated the eventual surgical response, the absolute blood-pressure values during long-term captopril related well with those after operation. Pretreatment plasma renin and angiotensin II concentrations, while closely predicting the immediate captopril response, are fallible guides to surgical prognosis. In contrast, long-term treatment with converting-enzyme inhibitors may provide an accurate indication of surgical outcome.

Adolescent↗
PubMed1982

Relation of arterial pressure with body sodium, body potassium and plasma potassium in essential hypertension.

1. Exchangeable sodium (NaE), plasma electrolytes and arterial pressure were measured in 121 normal subjects and 91 patients with untreated essential hypertension (diastolic greater than 100 mmHg), 21 of whom had low-renin hypertension. Plasma concentrations of renin, angiotensin II and aldosterone were measured in all hypertensive patients, total body sodium, total body potassium and exchangeable potassium (KE) in some patients. 2. Mean NaE was not different in normal and hypertensive subjects provided the two groups were matched for leanness index. In the subgroup of young hypertensive patients aged 35 years or less mean NaE was below normal. NaE was not related to arterial pressure in normal subjects but in hypertensive patients there were positive and significant correlations of arterial pressure with NaE and with total body sodium. 3. NaE and total body sodium increased with age in hypertensive but not in normal subjects. Partial regression analysis suggested that the correlation of NaE with arterial pressure was not explained by an influence of age. 4. Mean NaE was not increased and mean KE was not decreased in patients with low-renin hypertension. 5. Plasma potassium concentration, KE and total body potassium correlated inversely and significantly with blood pressure in hypertensive patients. These correlations were more marked in young than in old patients. 6. Multiple regression analysis showed that the combination of NaE and plasma potassium concentration 'explained' more of the variation of systolic blood pressure in hypertensive patients than it did in normal subjects. Plasma potassium concentration 'explained' more of the variation in young hypertensives and NaE 'explained' more in older patients. 7. Our findings suggest than changes of plasma and body potassium are important in the earlier stages of essential hypertension and that changes of body sodium become important later.

Adult↗
PubMed1982

Response of the renin-angiotensin-aldosterone system to upright tilting and to intravenous frusemide: effect of prior metoprolol and propranolol.

1 Upright tilting in normal volunteers caused increases in plasma active and total renin, angiotensin II and aldosterone; a slight but significant fall in inactive renin accompanied these changes. 2 The alterations in the renin-angiotensin-aldosterone system on tilting took up to 1 h upright to become fully established. 3 Large intravenous doses of propranolol or metoprolol attenuated, without abolishing, the rises in active renin, angiotensin II, and aldosterone; the attenuation was most evident soon after tilting and was largely overcome by 1 h upright. Inactive renin did not fall significantly after beta-adrenoceptor blockade. 4 Intravenous frusemide caused immediate rises in plasma active, total and inactive renin, angiotensin II, and aldosterone, which then declined over 2 h despite increasing cumulative sodium losses. 5 Intravenous propranolol or metoprolol attenuated, without abolishing, these early increases in the components of the renin-angiotensin-aldosterone system after frusemide. 6 Prior oral metoprolol or propranolol, while significantly slowing the heart, did not limit the early rise in plasma angiotensin II following intravenous frusemide. 7 Thus in contrast to previous workers, we did not find that propranolol eliminated the response of the renin-angiotensin system to upright tilting; in part this difference appeared to be due to the longer tilt we employed. 8 Also in contrast to earlier work, we found attenuation by both intravenous propranolol and metoprolol of the immediate rise in renin after intravenous frusemide.

Adrenergic beta-Antagonists↗