A. M. M. Cumming

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.

Body Elemental Composition, with Particular Reference to Total and Exchangeable Sodium and Potassium and Total Chlorine, in Untreated and Treated Primary Hyperaldosteronism

The whole body content of sodium, potassium, chlorine, calcium, phosphorus and nitrogen was measured by neutron activation analysis in 13 patients with untreated primary hyperaldosteronism (Conns syndrome; aldosterone-secreting adenoma). Concurrently, exchangeable sodium and potassium were estimated by isotope dilution. Results were compared with values in the same patients during treatment with potassium-conserving diuretics and again after removal of the adenoma; and also with those in a series of 30 patients having untreated essential hypertension. Both total body and exchangeable sodium were high in Conns syndrome before treatment and were reduced by spironolactone or amiloride and by subsequent surgery. There was no evidence of alteration in the proportion of non-exchangeable sodium in this disease, in contrast to earlier reports. Total body and exchangeable potassium were low in untreated Conns syndrome and increased to normal after therapy: the proportion of non-exchangeable potassium was similar before and after treatment, and also similar to that in essential hypertension. Total body chlorine was increased before treatment in Conns syndrome and returned to normal with therapy; body calcium, phosphorus and nitrogen were normal throughout.

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.

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 Conns syndrome. In renal artery stenosis the inverse correlation could result from a natriuretic effect of increased arterial pressure occurring mainly in the contralateral kidney.

IS THE ‘SODIUM INDEX’ A USEFUL WAY OF EXPRESSING CLINICAL PLASMA RENIN, ANGIOTENSIN AND ALDOSTERONE VALUES?

In normal subjects taking variously high, normal or low sodium diets, while potassium intake was maintained within the normal range, highly significant inverse relationships were demonstrated between 24 h urinary sodium output and the concurrent plasma concentrations of renin, angiotensin II and aldosterone. With linear coordinates, these relationships were described by rectangular hyperbolae. With logarithmic plots the relationships became rectilinear. When 24 h urinary sodium output was 75 mmol or higher, there was no worthwhile advantage in relating renin to sodium excretion; plasma angiotensin II and aldosterone, however, were significantly related inversely to urinary sodium in this range. When 24 h urinary sodium output was below 10 mmol, plasma renin, angjotensin II and aldosterone all varied over wide but elevated ranges and were not significantly related to urinary sodium excretion rates. We conclude that whereas estimations of urinary sodium may be of value in revealing latent aberrations of sodium intake, there is no distinct advantage in relating measurements of renin or angiotensin II to urinary sodium output if the diet is known to be within broad ‘normal’ limits. This should simplify the relevant blood sampling procedure under both ward and outpatient conditions. If plasma renin, angiotensin II and aldosterone are to be related to concurrent urinary sodium output, logarithmic, rather than linear, co‐ordinates, are appropriate.

Onset of action of captopril, enalapril, enalaprilic acid and lisinopril in normal man

SummaryThe effects of orally administered captopril, enalapril and lisinopril on plasma concentrations of angiotensin converting enzyme (ACE), angiotensin II (ANGII) and renin (PRC) were studied over a period of 6 hours in 6 normal subjects. A further 4 subjects received intravenous enalapril and enalaprilic acid (enalaprilat). Captopril (25 mg) by mouth caused a fall in pANGII that reached a nadir 30 to 40 minutes after administration but an effect was hardly apparent after 6 hours. Enalapril (10 mg) by mouth had less marked effects on pACE and pANGII with a decline in levels first apparent 1 hour after administration and the lowest levels reached between 3 and 6 hours. Lisinopril (10 mg) produced a progressive fall in pACE and pANGII from 1 hour to reach the lowest values 6 hours after treatment. Intravenous enalaprilat (5 mg) produced an immediate sustained fall in both pACE and pANGII but intravenous enalapril (7 mg) had a biphasic inhibitory effect.

PRE‐OPERATIVE LOCALIZATION OF ALDOSTERONE‐SECRETING ADRENAL ADENOMAS

Techniques for pre‐operative localization of aldosterone‐secreting adrenal adenomas were studied in thirty‐seven patients, each with hypertension and biochemical evidence of primary hyperaldosteronism and each later having adrenal surgery (thirty‐two adenomas, five bilateral adrenal hyperplasia).