J. I. S. Robertson

PLASMA RENIN, RENIN SUBSTRATE, ANGIOTENSIN II, AND ALDOSTERONE IN HYPERTENSIVE DISEASE OF PREGNANCY

Abstract Plasma concentrations of renin, renin substrate, angiotensin II, and aldosterone were measured in the peripheral venous blood of women with hypertension and proteinuria in late pregnancy and in a control group of normal pregnant women matched for age, parity, time of gestation, and posture. All four substances were found to be significantly lower in the hypertensive group as compared with normal pregnancy. Therefore, raised circulating levels of renin, renin substrate, angiotensin II, and aldosterone cannot be invoked in the pathogenesis of pregnancy hypertension. This suppression of the renin-angiotensin-aldosterone system in hypertensive disease of pregnancy could represent an adjustment to an increase in the circulating level of some unidentified pressor agent or mineralocorticoid.

ABNORMAL RELATION BETWEEN EXCHANGEABLE SODIUM AND THE RENIN-ANGIOTENSIN SYSTEM IN MALIGNANT HYPERTENSION AND IN HYPERTENSION WITH CHRONIC RENAL FAILURE

Abstract Exchangeable sodium and plasma levels of renin and angiotensin II were measured in patients with normal blood-pressure and in patients with hypertension, either in the malignant phase or associated with chronic renal failure. In normotensive subjects exchangeable sodium correlated inversely with plasma-renin concentration and with plasma-angiotensin-II. Abnormally high levels of renin and angiotensin II, relative to exchangeable sodium, were found in the hypertensive patients. This accords with the suggestion that renin release, inappropriately high in relation to sodium balance, may raise blood-pressure in certain types of hypertension.

PSYCHIATRIC DISTURBANCE LEADING TO POTASSIUM DEPLETION, SODIUM DEPLETION, RAISED PLASMA-RENIN CONCENTRATION, AND SECONDARY HYPERALDOSTERONISM

Abstract Nine psychiatrically disturbed women were studied, variously suffering from the effects of anorexia nervosa, vomiting, and abuse of diuretics and purgatives. Each had more than one source of electrolyte depletion, and each deliberately concealed at least one of these. All were potassium-depleted, and in all but one sodium depletion was also evident. During exacerbations plasma-renin concentration was raised, secretion-rate and plasma concentration of aldosterone were increased, and the metabolic clearance of aldosterone was diminished. It is suggested that in combined sodium and potassium deficiency, conservation of sodium may be relatively more effective than that of potassium, and that multiple routes of electrolyte loss prevent effective homœostasis.

IS LOW-RENIN HYPERTENSION A STAGE IN THE DEVELOPMENT OF ESSENTIAL HYPERTENSION OR A DIAGNOSTIC ENTITY ?

A study of the frequency distribution of plasma-renin concentration in 81 patients with essential hypertension produced no evidence of a distinct sub-population with low renin levels. An arbitrary dividing line was used, therefore, to define low-renin hypertension (36% of patinets). Patients in this group were older than those with normal renin levels, and there was a significant negative correlation between renin and age among all patients. Low-renin hypertension was not characterized by increased exchangeable sodium, but exchaneable postassium was significantly lower than in patients with normal plasma-renin. This difference became insignificant when five patients in the low-renin group with persistent hypokalaemia were excluded. It is concluded that low-renin hypertension does not represent a separate diagnostic entity but that plasma-renin falls with age in essential hypertension.

HYPERTENSION AND SECONDARY HYPERALDOSTERONISM ASSOCIATED WITH A RENIN-SECRETING RENAL JUXTAGLOMERULAR-CELL TUMOUR

Abstract A case of renin-secreting renal juxtaglomerular-cell tumour is described in an 8-year-old child. Severe hypertension associated with hypokalaemia was accompanied by raised plasma concentrations of renin, angiotensin II, and aldosterone in peripheral blood. The secondary hyperaldosteronism was shown not to be due to the malignant phase or to renal-artery stenosis. The tumour was lateralised by the demonstration of higher concentrations of renin and angiotensin II in left than in right renal venous plasma, and visualised on selective renal arteriography. The patient showed much greater elevation of blood-pressure and plasmaaldosterone than normal subjects infused with angiotensin to produce comparable plasma-angiotensin-II levels. Before operation, both head-up tilting and dietary sodium restriction caused a further striking increase of peripheral renin and angiotensin II. The hypertension and biochemical abnormalities were all relieved by removal of the affected kidney. The tumour had a very high content of renin. Extreme care is necessary in interpreting minor differences in renin level in renal veins if false-positive or falsenegative diagnoses are to be avoided.

MICROANGIOPATHIC HÆMOLYTIC ANÆMIA AND THE PATHOGENESIS OF MALIGNANT HYPERTENSION

Abstract The relation between severe hypertension and microangiopathic haemolytic anaemia (M.H.A.) was explored in detail in nine patients with both conditions. Blood-films were also examined in eighty-seven cases of hypertension. Of twenty-four patients with malignant-phase hypertension, sixteen had evidence of M.H.A.: of the remaining patients none had evidence of M.H.A. A hypothesis is suggested for the relation between M.H.A. and malignant hypertension in which the following are the important steps: high arterial pressure or primary vascular disease increases the permeability of small blood-vessels to fibrinogen; fibrin is deposited in the wall and lumen of vessels, and persists either because the deposition of new fibrin is increased or because fibrinolysis is impaired; fibrin deposits fragment red blood-cells, leading to haemolysis and further deposition of fibrin.

APPARENTLY ISOLATED EXCESS DEOXYCORTICOSTERONE IN HYPERTENSION: A Variant of the Mineralocorticoid-excess Syndrome

Abstract Plasma-deoxycorticosterone (DOC) concentration was measured in thirty-one hypertensive patients, all with normal plasma-aldosterone values. Plasma-Doc concentration was persistently high in six of the twenty-one patients with low plasma-renin concentration and in none of the ten cases in whom renin values were normal. There were intermittently raised DOC levels in three further patients with low plasma-renin and in two cases in the normal-renin group. Intermittent hypo- kalaemia was observed in each of the cases with persistently raised plasma-DOC. The possible role of raised DOC levels in the pathogenesis of hypertension and in the suppression of the renin-angiotensin system is discussed.

RENAL ABNORMALITY OF ESSENTIAL HYPERTENSION

Abstract Although homœostatic mechanisms relate sodium balance, renin, and arterial pressure, the reduction of renin sometimes seen in essential hypertension cannot be attributed to abnormal sodium retention. It is proposed instead that renin decreases and sodium status remains normal because the pressure-natriuretic mechanism within the kidney is reset by increased filtration fraction. Neurogenic factors may raise blood-pressure and cause resetting by some other means at an early (labile) stage of essential hypertension, but, once filtration fraction is raised and remains elevated on withdrawal of the neurogenic component, essential hypertension will have a renal cause. A similar mechanism may account for the failure of secondary hypertension to fall when its cause is removed.

The treatment of low-renin (“primary”) hyperaldosteronism

Abstract Sixty-four patients with low-renin (“primary”) hyperaldosteronism underwent adrenal surgery. A unilateral adrenocortical adenoma was found in 48; no tumor was identified in 14, the adrenal glands then usually showing hyperplasia of the zona glomerulosa. The adrenal lesion in two further patients was difficult to classify. There was a significant fall in systolic and diastolic blood pressure after operation in both the adenoma and hyperplasia groups, although the fall in diastolic pressure was significantly greater in the adenoma group. Blood pressure fell to an arbitrary normal level in 56 per cent of patients with adenoma and in 15 per cent of patients in the hyperplasia group. Ninety-five patients with primary hyperaldosteronism received spironolactone for a minimum period of four weeks. There was a significant fall in mean systolic and diastolic pressure during treatment in both the adenoma and hyperplasia groups. However, the fall in diastolic pressure was again significantly greater in the adenoma group. There was a significant positive correlation between the fall in blood pressure during spironolactone and following adrenal surgery. Eighteen patients also received amiloride preoperatively and again there was a significant fall in systolic and diastolic blood pressure, although levels were slightly higher than during spironolactone or after subsequent adrenal surgery. Nineteen patients received a two week course of dexamethasone, without effect on blood pressure or the electrolyte abnormalities. It is suggested that removal of the tumor-bearing gland is usually the treatment of choice for patients with an aldosterone producing adenoma, provided preoperative spironolactone has reduced blood pressure to normal or near normal. However, long-term spironolactone is an acceptable alternative. For patients in the hyperplasia group, long-term spironolactone is usually the treatment of choice. If this drug is not tolerated, amiloride may be substituted. If preoperative spironolactone does not produce a satisfactory hypotensive response, adrenal surgery is unlikely to do so and hypertension should be controlled with other conventional hypotensive drugs. All patients with primary hyperaldosteronism in whom an adrenocortical adenoma is not identified preoperatively should be screened for the rare glucocorticoid-remediable variant. Dexamethasone 1 to 2 mg. daily for two to four weeks will reverse the biochemical abnormalities and reduce blood pressure. When an adrenocortical carcinoma is suspected, prompt surgical excision is required.

PLASMA ELECTROLYTES, RENIN, AND ALDOSTERONE IN THE DIAGNOSIS OF PRIMARY HYPERALDOSTERONISM: With a Note on Plasma-corticosterone Concentration

Abstract Plasma electrolytes, renin, and aldosterone concentrations were measured in 50 patients with primary hyperaldosteronism. Although plasma-potassium concentration varied over a considerable range in most cases, the levels were consistently lower than 3·7 meq. per litre in 27 patients, and intermittently so in all but 1 of the remainder. It is particularly important to avoid forearm exercise immediately before venepuncture if falsely high potassium values are to be avoided. Plasma-renin concentration was subnormal at least once in 42 patients, and consistently so in 24 of these. The remaining results were normal, most of them falling near the lower limit observed in normal subjects. In several cases sodium restriction caused distinct increases in plasma-renin concentration, and in 1 patient the final level was within the range found in sodium-deprived normal subjects. Plasma-aldosterone concentration was abnormally high on at least one occasion in 38 of the 39 patients in whom it was measured.