D. L. Davies

Comparison of surgery and prolonged spironolactone therapy in patients with hypertension, aldosterone excess, and low plasma renin.

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery. Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment. In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied. Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped. In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.

PLASMA RENIN CONCENTRATION IN HUMAN HYPERTENSION. 1. RELATIONSHIP BETWEEN RENIN, SODIUM, AND POTASSIUM.

be only a measure of mucosal damage. In this connexion it is worth mentioning that the small-intestinal mucosa is frequently abnormal in ulcerative colitis, and the degree of abnormality is positively correlated with the clinical severity of the colitis (Salem et al., 1964, 1965). This raises the possibility that absorption of whole protein may occur from the small intestine, with resulting high levels of antibody that are then no more than an indication that the intestine has been widely affected, which in turn may indicate a relatively bad prognosis. Circulating antibodies to dietary proteins are present from birth and can be demonstrated in cord blood, commonly at a higher titre than in maternal blood (Wright et al., 1962). When infants are weaned and fed on cows milk the levels of circulating antibodies to cows-milk proteins rise considerably (Gunther et al., 1962). In ulcerative colitis, in coeliac disease, and in idiopathic steatorrhoea the titre of circulating antibodies to various dietary proteins are often high (Taylor and Truelove, 1961 ; Taylor et al., 1961, 1964). So far as ulcerative colitis is concerned, early weaning from the breast was found to be twice as common in the subjects of this disease as in control subjects (Acheson and Truelove, 1961). There is the possibility that immunological stimulation by dietary proteins during infancy may set the stage for a variety of diseases in later life and that ulcerative colitis is one of them.

Weight reduction in a blood pressure clinic.

Forty-nine hypertensive patients who were overweight were randomly allocated to one of three strategies for attaining weight reduction and were followed for one year. Those referred to a dietitian lost more weight (mean 5.1 kg) than those given a diet sheet (mean 2.64 kg) or simply advised by the doctor to reduce weight (mean 2.15 kg). One-third of all the patients lost 6 kg or more. Successful weight loss was associated with a highly significant and substantial improvement in blood pressure control and with less frequent increases in antihypertensive treatment.

Sodium and potassium in essential hypertension.

A study was carried out of arterial pressure and body content of electrolytes in 91 patients with essential hypertension and 121 normal controls. Exchangeable sodium was found to be positively correlated with arterial pressure in the patients, the correlation being closest in older patients; values of exchangeable sodium were subnormal in young patients; and plasma, exchangeable, and total body potassium correlated inversely with arterial pressure in the patients, the correlations being closest in young patients. Three hypotheses were proposed to explain the mechanisms relating electrolytes and arterial pressure in essential hypertension--namely, a cell-salt hypothesis, a dietary salt hypothesis, and a kidney-salt hypothesis. It was concluded that two mechanisms probably operate in essential hypertension. In the early stages of the disease blood pressure is raised by an abnormal process related more closely to potassium than to sodium. A renal lesion develops later, possibly as a consequence of the hypertension. This lesion is characterised by resetting of pressure natriuresis and is manifest by an abnormal relation between body sodium and arterial pressure and by susceptibility to increased dietary sodium intake.

Results of adrenal surgery in patients with hypertension, aldosterone excess, and low plasma renin concentration.

Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery. There was a highly significant fall in mean systolic and diastolic pressures after the operation. The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients. There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.

Hyponatraemic hypertensive syndrome with renal-artery occlusion corrected by captopril.

Malignant hypertension with severe hyponatraemia, hypokalaemia, depletion of sodium and potassium, and elevated blood levels of renin, angiotensin I, angiotensin II, aldosterone, and arginine vasopressin developed in a woman with renal-artery occlusion. Plasma angiotensin II was disproportionately high in relation to exchangeable sodium. Captopril, by inhibiting conversion of angiotensin I to angiotensin II, further elevated the blood levels of renin and angiotensin I but corrected all other abnormalities. Unilateral nephrectomy was subsequently curative.

Variations in Plasma Renin During the Menstrual Cycle

Intravenous infusions of renin or angiotensin stimulate aldosterone secretion and excretion (Laragh et al., 1960 ; Genest et al., 1961 ; Carpenter et al., 1961 ; Blair-West et al., 1962). The concentration of renin in plasma varies in several physiological and pathological states (Brown et al., 1964a) in a way which supports the suggestion (Gross, 1958 ; Davis et al., 1961) that the renin-angiotensin system might regulate aldosterone secretion. As the urinary excretion of aldosterone varies during the menstrual cycle (Reich, 1962 ; Nowaczynski et al., 1962), the present study was undertaken to determine whether these changes might be accompanied by variations in plasma renin.

HORMONES AND HYPERTENSION

It seems clear that hypertension may be a common feature of growth hormone excess, but precise frequency figures cannot be derived from current data due to bias and inadequate epidemiological study techniques. The mechanism of increased blood pressure is also unclear. There is clear evidence of gross sodium retention and hypertrophy of the heart and blood vessels but these occur in both normotensive and hypertensive acromegaly. This is also true of changes in body fluid volumes. Studies of changes in the levels of, and blood pressure sensitivity to, hormones such as ANF, angiotensin II and catecholamines are frequently contradictory and also difficult to interpret at present. The interrelationships between growth hormone, renal function and blood pressure require further careful study.

Falsely High Plasma Potassium Values in Patients with Hyperaldosteronism

The common practice of encouraging forearm exercise as an aid to venepuncture is a potent source of erroneously high plasma potassium levels. This may be sufficient to obscure a suspicion of hyperaldosteronism, with possible serious repercussions in hypertensive patients, in whom the diagnosis of hyperaldosteronism has important therapeutic implications. Plasma is preferable to serum for potassium estimations, and forearm exercise should be avoided before venepuncture for potassium measurements.

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.