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Biomedical subjects

A F Lever

Publications and source records attributed to A F Lever.

At least 127 records · Page 7Linked to original sources
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

Peptide inhibitors of renin.

Three experiments are described using new substrate analogue inhibitors of renin. The first experiment shows that introduction of a reduced isostere in the scissile peptide bond of an analogue greatly increases its ability to inhibit renin of a particular species. However, different species of renin substrate have different amino acids in their scissile bond and variation here also greatly influences the affinity of renin and substrate and hence of renin and substrate analogues. Finally, substitution of amino acids in the C-terminal adjacent to the scissile bond influences the affinity and efficacy of substrate analogues as inhibitors. In our second experiment a peptide inhibitor of dog renin, H.77, was used in an affinity column to produce a one-stage, 2000-fold, and complete purification of human renin. In our third experiment infusion of H.77 was used to lower circulating concentrations of angiotensin I and angiotensin II in conscious sodium-deplete dogs. Captopril was then given in addition to H.77 but blood pressure did not fall further, suggesting that captopril lowers blood pressure wholly or partly by reducing angiotensin II within the circulation and in extravascular sites.

Amino Acid Sequence↗
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

10. Hypertension. A comparison of the effects of angiotensin II infusion and variations in salt intake on plasma aldosterone levels in normal subjects, patients with essential hypertension and patients with hyperaldosteronism.

Infusion of angiotensin II into a patient with dexamethasone-suppressible hyperaldosteronism caused a brisk increase in plasma aldosterone concentration. In this behaviour, the patient resembled those patients with idiopathic hyperaldosteronism rather than those with tumorous primary hyperaldosteronism. Sodium depletion of a small group of patients with mild essential hypertension elicited a spectrum of increases in plasma aldosterone levels ranging from zero to normal. Angiotensin II infusion in both sodium replete and deplete states also caused variable aldosterone responses. These results suggest that the derangement of adrenal function in this condition varies continuously in severity.

Adrenocorticotropic Hormone↗
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↗
PubMed1983

Effects of prolonged and brief infusions of noradrenaline on arterial pressure and on the plasma concentrations of active renin, angiotensin II, aldosterone and potassium.

Conscious male beagle dogs were given constant intravenous infusions of noradrenaline for 14 days, four receiving 125 ng/kg/min and four 250 ng/kg/min. Before, during and after these infusions dose-response studies were done in which additional noradrenaline was infused at 500, 1000 and 2000 ng/kg/min, each rate for 1 h. Blood samples were taken before and during infusions for measurement of haematocrit and plasma concentrations of noradrenaline, active renin, angiotensin II, aldosterone, sodium and potassium. Fourteen-day infusion of noradrenaline at 125 ng/kg/min did not raise blood pressure significantly though infusion at 250 ng/kg/min did, but for the first week of infusion only. Heart rate decreased significantly at both rates. Arterial pressure fell markedly and significantly on stopping infusion. Mean plasma concentrations of renin, angiotensin II and aldosterone tended to be lower during prolonged infusion of noradrenaline, but only the fall of renin during the second week was significant in one group of dogs. Noradrenaline at higher rates significantly raised blood pressure and increased plasma concentrations of renin and angiotensin II. Plasma aldosterone concentration did not rise significantly, perhaps because plasma potassium concentration decreased; in support of this theory changes of plasma aldosterone correlated with changes of plasma potassium but not with changes of angiotensin II. The rise in arterial pressure during dose-response studies was related to the increase of plasma noradrenaline. Prolonged infusion of noradrenaline did not alter the dose-response relation between plasma noradrenaline concentration and arterial pressure.

Aldosterone↗
PubMed1982

Converting-enzyme inhibitor enalapril (MK421) in treatment of hypertension with renal artery stenosis.

Enalapril maleate (MK421), a new inhibitor of angiotensin converting enzyme, in single daily doses of 1.25-40 mg was assessed in five patients with hypertension and renal artery stenosis. Only small falls in plasma angiotensin II concentrations were seen at doses less than 10 mg; even with 10 and 20 mg, angiotensin II concentrations had risen again 24 hours from the last dose. During long-term treatment with 10-40 mg daily all patients achieved good blood-pressure control. No significant changes of body sodium or potassium values were seen. The drug was well tolerated with no serious side effects. These findings are evidence of the efficacy and acceptability of enalapril in the medical management of hypertension with renal artery stenosis.

Adult↗
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

Captopril treatment: inter-dose variations in renin, angiotensins I and II, aldosterone and blood pressure.

1 The ability of captopril, 150 mg three times daily by mouth, to effect sustained reduction in plasma angiotensin II, with converse increases in circulating angiotensin I, and in active, inactive and total renin concentrations, has been assessed. 2 During prolonged treatment with captopril alone, and 12 h after the last dose of the drug, plasma angiotensin II remained approximately one-sixth of basal concentrations, while angiotensin I and renin concentrations were proportionately increased. However, further increases in angiotensin I, and in active, inactive and total renin concentrations, were seen 2 and 6 h after the morning dose of 150 mg captopril. 3 Inter-dose variations in plasma aldosterone and blood pressure were not closely related to concurrent variations in the renin-angiotensin system. 4 Arguments are presented for relying on measurements of plasma renin and angiotensin concentrations rather than of renin activity or aldosterone in assessing the effectiveness of converting enzyme inhibition.

Adolescent↗
PubMed1982

Intravenous labetalol in the treatment of severe hypertension.

1 We have compared, in patients with severe hypertension, the administration of intravenous labetalol by single rapid injection, by repeated bolus injections, and by incremental infusion. 2 Incremental infusion was the most consistently (albeit not invariably) effective method, and that least prone to cause side-effects. 3 An occasional very marked decrease in blood pressure was seen with all these techniques but least often with incremental infusion. Thus close and continuous supervision is mandatory. 4 All three methods produced slight but significant decreases in heart rate, and in plasma angiotensin II and aldosterone. 5 Intravenous labetalol was also effective in controlling hypertensive crises of phaeochromocytoma and those following the withdrawal of clonidine. 6 In a total of 70 severely hypertensive patients given intravenous labetalol, none showed adverse neurological or cardiological sequelae.

Adrenal Gland Neoplasms↗
PubMed1982

Whole body elemental composition in patients with essential hypertension.

The whole body content of sodium, chlorine and potassium has been measured in 30 patients with essential hypertension, using the techniques of in vivo neutron activation analysis and whole body counting. Total exchangeable sodium and potassium were also measured, and found to be well correlated with the total body amounts of these elements. Comparable measurements on normotensive subjects could not be obtained, but results for both elements were similar to those expected on the basis of published values for healthy normal body composition. Similarly, no abnormality was found in the average body content of the other major elements (chlorine, calcium, phosphorus and nitrogen). We therefore have no evidence that essential hypertension is associated with any abnormality in the mean body content of these elements. However, there was some evidence of a relationship between body sodium and blood pressure in this study group.

Adult↗