D.G. Beevers

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.

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.

BLOOD-LEAD AND HYPERTENSION

Blood and tap-water lead levels were examined in 135 hypertensives and 135 age and sex matched normotensives. Among male hypertensives there was a significant excess of cases with high blood-lead levels and a similar but statistically non-significant trend was found amongst female hypertensives. A positive correlation was found between blood-lead and tap-water lead. It is concluded that in the West of Scotland high blood-pressure is associated with high blood-lead levels, which might explain the high prevalence of cardiovascular disease in the area.

BODY-FLUID VOLUME IN LOW-RENIN HYPERTENSION

Abstract Plasma and extracellular-fluid volumes were normal in thirty-eight patients with normal-renin hypertension and in seventeen patients with low-renin hypertension, there being no difference between the two groups. This strongly suggests that reduction of renin in low-renin hypertension is not brought about by sodium retention with volume expansion.

Sodium and the renin-angiotensin system in essential hypertension and mineralocorticoid excess.

Abstract Exchangeable sodium (NaE) was increased in untreated primary hyperaldosteronism but normal in treated primary hyperaldosteronism and in untreated essential hypertension, low-renin hypertension, and hypertension with excess 11-deoxycorticosterone ( D OC). The relation between NaE and plasma-renin was normal in essential hypertension and primary hyperaldosteronism but subnormal in low-renin hypertension and DOC excess. Depression of renin in low-renin hypertension cannot therefore be attributed to abnormal sodium retention.

Blood-cadmium in hypertensives and normotensives.

70 hypertensive patients and 70 controls matched for age and sex were investigated for a possible relationship between blood-cadmium and hypertension. No significant differences between the two groups were detected, although the blood-cadmium level was significantly higher in smokers as compared to non-smokers. These data do not support the hypothesis that cadmium is involved in the development of hypertension in man.

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.

Salt and blood pressure in Scotland.

Dietary salt intake and urinary sodium excretion were compared in normotensive and hypertensive subjects in Renfrew, Scotland. All groups had high 24-hour urinary salt excretions, and hypertensive subjects did not eat or excrete more salt than normotensive subjects. The only significant relations found were a lower sodium excretion in hypertensive women than in normotensive women (p < 0.02) and a lower urinary sodium concentration in hypertensive men than in normotensive men (p < 0.05). These data provide no support for the hypothesis that dietary salt is a major cause of hypertension.

Low-renin (“primary”) hyperaldosteronism: Differential diagnosis and distinction of sub-groups within the syndrome

Abstract Hypokalemia in a hypertensive patient is commonly diuretic-induced. However, if hypokalemia persists after stopping diuretic therapy, possible mineralocorticoid excess, including primary hyperaldosteronism, must be considered. Hypertension with secondary hyperaldosteronism may occur with malignant-phase hypertension and with renal or renovascular disease. However, secondary hyperaldosteronism is associated with raised circulating levels of renin and angiotensin II, while in primary hyperaldosteronism plasma concentrations of renin and angiotensin II are inappropriately low. Hypertension and hypokalemia may also be associated with an excess of a mineralocorticoid other than aldosterone. Syndromes associated with an apparently isolated excess of 11-deoxycorticosterone, of 18-hydroxy-11-deoxycorticosterone and of corticosterone have been described. Plasma renin may be suppressed as in primary hyperaldosteronism, but aldosterone values are normal or low. Hypertension, hypokalemia, and renin suppression may also occur in Cushings syndrome, associated with abnormalities of corticosteroid synthesis and during ingestion of licorice-containing drugs. Again, aldosterone values are normal or low. Once the diagnosis of primary hyperaldosteronism has been confirmed, the rare cases of glucocorticoid-remediable hyperaldosteronism and hyperaldosteronism associated with adrenal or ovarian carcinoma must be excluded. There-after, it is necessary to distinguish between the two commonest forms, a unilateral adrenocortical adenoma and bilateral hyperplasia of the zona glomerulosa. The statistical technique of quadric analysis used prospectively has correctly predicted adrenal pathology in 23 of 24 patients. Other methods for differentiating the two groups include comparisons of aldosterone response to sodium loading, comparison of postural and diurnal changes in plasma aldosterone, adrenal venography, and examination of the adrenal glands by ultrasound and by scintillation scanning.

The prevalence of hypertension in an unselected population, and the frequency of abnormalities of potassium, angiotensin II and aldosterone in hypertensive subjects.

SummaryAn epidemiological survey amongst 3,001 subjects between the ages of 45 and 64 in the Burgh of Renfrew, Scotland, revealed that 468 (15.6 %) subjects had a diastolic blood pressure of 100 mmHg or more. Examination of the General Practitioners medical records of those subjects whose diastolic blood pressure was less than 100 mmHg revealed 55 subjects who were receiving antihypertensive treatment and a further 113 subjects who were receiving no antihypertensive therapy, but who had previously been recorded as having a blood pressure above this level (Total 636 ; 21.2 % of survey).Investigation of the severest cases of hypertension has demonstrated no cases of primary hyperaldosteronism and a frequency distribution curve for plasma angiotensin II concentration among this group shows no evidence of a subpopulation of subjects with low levels.