Functional tests for primary aldosteronism: Value of captopril suppression

With the introduction of more simple screening tests such as the aldosterone/renin ratio, the detection rate of primary aldosteronism has increased considerably. Until now, no reference values have been available for reporting the aldosterone/renin ratio using plasma aldosterone values expressed in SI units (pmol/L) and plasma active renin (ng/L) measured by immunoradiometric assay. We studied 153 subjects who had either normal blood pressure, essential hypertension, or primary aldosteronism. Essential hypertensive patients usually have aldosterone/renin (pmol/ L/ng/L) ratios below 100, whereas ratios for patients with primary aldosteronism are above 140. Results that fall between 100 and 140 suggest a need for repeat testing. Patients with elevated aldosterone/renin ratios require confirmatory testing to demonstrate nonsuppressive autonomous aldosterone production. To this end, salt loading is widely used, but this approach may be contraindicated in patients with severe hypertension. The captopril suppression test appears as effective as salt loading in confirming a diagnosis of primary aldosteronism. In addition, the captopril test is safe, well tolerated, and cost-effective.     

Is there a relation between the renin-angiotensin-aldosterone system and vasopressin secretion in essential hypertension?

103 patients with mild or moderately severe essential hypertension and 35 healthy normotensive subjects were examined. In all patients examined plasma osmolality, plasma renin activity and plasma level of vasopressin and aldosterone were estimated twice: first after administration of a diet with a sodium chloride content of 100 to 120 mmol/a day and 8 hours recumbency and a second time after 3 days of dietary sodium chloride restriction (20 mmol/a day) and 3-4 hours upright position. In hypertensives independent of the behaviour of the plasma renin activity similar values of the plasma osmolality, the plasma level of vasopressin and the aldosterone level could be established as in healthy persons. In contrast to normals in hypertensive subjects no significant correlation between plasma osmolality or plasma renin activity and plasma level of vasopressin and aldosterone was stated. In spite of normal levels of vasopressin and aldosterone a significant correlation between the plasma level of vasopressin and aldosterone and the systolic blood pressure was found in hypertensive patients. From the results obtained in this study follows that in hypertensive patients the plasma osmolality is only of secondary importance for the secretion of vasopressin and aldosterone and for the plasma renin activity. The importance of plasma vasopressin and aldosterone in the pathogenesis of hypertension seems to be probable but not yet unanimously proved.     

Diagnostic value of the post-captopril test in primary aldosteronism

Primary aldosteronism is a disorder with hypertension, hypokalemia, increased plasma aldosterone, and suppressed renin activity. A random plasma aldosterone/renin activity (PA/PRA) >65 (conventional units ratio [CUR] >30) has been proposed as a screening test. We have retrospectively determined the value of the post-captopril plasma aldosterone/renin activity (CAPT PA/PRA) test for the diagnosis of patients with primary aldosteronism whose PA/PRA was <65. We considered the CAPT PA/PRA test to be positive for primary aldosteronism if either the plasma aldosterone concentration did not drop below 0.33 nmol/L (12 ng/dL) or the ratio was >26 (CUR >12). We found 6 patients with a random PA/PRA of 21 to 60 (CUR 10 to 28), yet with an abnormal post-captopril test criteria for primary aldosteronism. Five had an abnormal saline suppression test, and all 6 were confirmed by a combination of diagnostic localization with computerized axial tomography, iodocholesterol scan, adrenal venous sampling, and/or surgery. Four had idiopathic adrenal hyperplasia, and 2 had an aldosterone-producing adenoma. One other patient had an abnormal random plasma aldosterone/renin activity ratio of 99 (CUR 46), a negative saline infusion study, and was determined to have essential hypertension. In summary, the CAPT PA/PRA, but not the random PA/PRA, correctly diagnosed 6 patients with primary aldosteronism in our institution. An additional patient with essential hypertension was incorrectly diagnosed as having primary aldosteronism by the PA/PRA test. We conclude that the simple addition of 25 mg of captopril, taken orally 2 hours before sampling, enhances the accuracy for diagnosing patients with primary aldosteronism.     

The Diagnostic Value of the 24 Hour Integrated Concentration of Plasma Aldosterone

The 24-hour urinary excretion rate of aldosterone, the 24-hour integrated concentration of plasma aldosterone (IC-ALDO) and the morning plasma aldosterone levels from a single, discrete venipuncture of 92 subjects (30 normal subjects, 62 patients with mild, essential hypertension) were compared, using the variance ratio method, to 12 patients with primary aldosteronism.

The variance of the IC-ALDO was significantly lower than the respective variances of the 24-hour urinary excretion of aldosterone (P < 0.01) and of the discrete, morning plasma levels of aldosterone (P < 0.01).

The clinical usefulness of this diagnostic procedure depends on its ability to discriminate between healthy subjects and various hypertensive patients. Because of its narrower variance and enhanced discriminatory ability, the 24-hour IC-ALDO may have useful application in diagnosis of various disorders of aldosterone secretion. We have found the IC-ALDO completely separated 11 of 12 primary aldosteronism patients (mean 36±17) from essential hypertensive controls (mean 9.6±4.1)(P < 0.01). When IC-ALDO was combined with integrated concentration of plasma renin activity in an ALDO/RENIN ratio, all 12 primary aldosteronism patients were diagnosed.     

Effects of a single administration of captopril on hemodynamics and serum angiotensin converting enzyme activity, plasma renin activity and plasma aldosterone concentration in hypertensive patients

Hemodynamic responses and behaviors of the renin-angiotensin-aldosterone system to a single administration of captopril (50 mg) were studied in 16 hypertensive patients (essential hypertension, n = 10; renovascular hypertension, n = 3; primary aldosteronism, n = 2; Cushing's syndrome, n = 1). In 10 essential hypertensive patients, the immediate blood pressure reduction caused by decreased total peripheral resistance after the administration of captopril was observed without changes of cardiac output and heart rate. Serum angiotensin converting enzyme activity and plasma aldosterone concentration significantly decreased, whereas plasma renin activity significantly elevated 2 hours after the administration of captopril. The close relationship between the pretreatment value of plasma renin activity and the maximum decrease in mean blood pressure in 16 hypertensive patients suggests that the depressor response to a single administration of captopril could evaluate the degree of angiotensin II dependency in the maintenance of high blood pressure in various types of hypertension.     

The captopril test for identifying renovascular disease in hypertensive patients

To develop a screening test for identifying renovascular hypertension, the blood pressure and plasma renin activity responses to an oral test dose of captopril were studied in 246 quietly seated hypertensive patients. The following criteria were developed that exploit the hyperresponsiveness of renin secretion in renovascular hypertensive patients: a 60-minute post-captopril plasma renin activity of 12 ng/ml per hour or more and an absolute plasma renin activity increase of 10 ng/ml per hour or more, along with a 150 percent increase in plasma renin activity (or a 400 percent increase if the baseline plasma renin activity was below 3 ng/ml per hour). Retrospectively, the test identified, among 200 hypertensive patients without evidence of renal dysfunction, all 56 patients with proved renovascular disease. In this group, false-positive results occurred only in two of 112 patients with essential hypertension and in six with secondary hypertension. Nine untreated patients had blood pressure levels of less than 160/100 mm Hg. The test was neither as sensitive nor specific in the 46 patients with renal insufficiency. This study demonstrates that the renin response to oral captopril is a useful screening test for identifying patients with unilateral or bilateral renovascular disease. Since the test also characterizes the renin dependency of the hypertension, it may have other diagnostic and therapeutic uses.     

Renin suppression by saline is blunted in nonmodulating essential hypertension

We have reported that 50% of subjects with normal renin essential hypertension have both delayed suppression of the renin-angiotensin-aldosterone axis following sodium infusion and a delayed rate of excretion of an acute salt load. In another study we have also described a subset of patients with essential hypertension (called nonmodulators) who have several abnormalities, including a pressor response to salt loading. To evaluate whether the abnormalities described in these different groups of patients actually occur in the same patient, we assessed the renin-angiotensin-aldosterone axis response to short-term saline loading in 38 hypertensive patients. Their ability to modulate was determined by their renal vascular response to infused angiotensin II on a high salt diet (200 mEq Na). In response to a 3-hour infusion of saline, 75 mEq/hr, the reduction in plasma renin activity at both 60 and 120 minutes was significantly greater (p less than 0.008) in patients with normal modulation than in the nonmodulators. Plasma aldosterone levels were also significantly lower (p less than 0.001) in those with intact modulation. Thus, nonmodulating essential hypertensive patients have abnormalities in several systems that influence sodium homeostasis, including altered adrenal and renal vascular response to angiotensin II, altered renal blood flow response to salt loading, and a delayed suppression of the renin-angiotensin-aldosterone system with short-term saline infusion.     

Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test.

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.     

Studies of renin and aldosterone in cirrhotic patients with ascites.

Plasma renin activity and aldosterone metabolism were investigated in patients with cirrhosis and refractory ascites. All patients initially showed marked elevations of plasma and renin activity and plasma aldosterone. Although metabolic clearance of aldosterone was reduced, increased secretion rate was the major factor leading to elevated plasma levels. The elevated plasma renin activity and plasma aldosterone were only minimally affected by posture, dietary sodium restriction, and diuretic administration, suggesting a near-maximal degree of secondary aldosteronism. In most patients plasma renin activity and plasma aldosterone returned to normal when spontaneous natriuresis appeared. However, in 2 patients during spontaneous diuresis and in all 3 given aminoglutethimide, sodium excretion was poorly correlated with plasma renin activity and plasma aldosterone, suggesting that other tubular and/or vascular factors are important in the intense sodium reabsorption found with cirrhosis and ascites.     

QT interval in patients with primary aldosteronism and low-renin essential hypertension

INTRODUCTION: QT interval prolongation increases the risk of sudden death in several medical conditions. Patients with primary aldosteronism and salt-sensitive hypertension experience more cardiovascular events than those with normal-renin essential hypertension. QT interval prolongation might represent one of the risk factors for cardiovascular events in these patients. The aim of the present study was to evaluate the QT interval in patients with primary aldosteronism and low-renin essential hypertension (LREH). METHODS: Twenty-seven patients with primary aldosteronism, 17 patients with LREH, 117 patients with essential hypertension and 25 healthy individuals were studied. Plasma aldosterone, plasma renin activity, and aldosterone to plasma renin activity ratio (ARR) were determined. Corrected QT intervals (QTcs) were measured from a 12-lead electrocardiogram. RESULTS: The QTc was longer in primary aldosteronism (434 +/- 23 ms) and LREH (430 +/- 18 ms) compared with essential hypertension (419 +/- 22 ms) and healthy controls (412 +/- 19 ms) (P = 0.0004). The prevalence of QTc longer than 440 ms was higher in primary aldosteronism (48%) and LREH (23%) compared with essential hypertension (11%) and healthy controls (4%) (P < 0.0001). QTc correlated with plasma aldosterone (P = 0.01), ARR (P = 0.02), and diastolic blood pressure (P = 0.01). ARR (P = 0.01) and systolic blood pressure (P = 0.01) were identified as independent predictors of QTc. CONCLUSIONS: We postulate that the elevated aldosterone secretion contributes to the prolongation of the QT interval in patients with primary aldosteronism and LREH through both a depletion of intracellular potassium concentration and higher blood pressure values. QTc measurement might represent one simple, non-invasive and reproducible index to characterize the cardiovascular risk in patients with primary aldosteronism and LREH.     

USE OF AN INTRAVENOUS SODIUM LOAD IN SCREENING FOR PRIMARY HYPERALDOSTERONISM

A sodium loading test was performed in 35 patients presenting with hypertension and hypokalemia. In 14 of these patients, intravenous administration of 0.9% saline (2 I in 4 h) on two consecutive days caused urinary aldosterone excretion to fall to values within the range for normal volunteers. The other 21 patients, in whom urinary aldosterone excretion did not decline following two days of saline loading, or in whom pronounced hypokalemia after the first day of loading precluded further saline infusion, were designated as having primary aldosteronism. Seventeen of this group underwent surgery and discrete adrenal adenomas were found in 16. When serum potassium concentration, plasma renin activity or the relationships of serum potassium to concurrent urinary potassium excretion or of urinary aldosterone excretion to plasma renin activity were used as alternative diagnostic criteria for primary aldosteronism, overlapping of the two groups occurred. It is concluded that measurement of urinary aldosterone excretion after intravenous sodium loading is a useful test in the identification of primary aldosteronism due to aldosterone-producing adenoma. In this series the saline loading test was more specific in diagnosis than criteria based on serum and urinary potassium, plasma renin activity or unsuppressed aldosterone excretion.     

Dysregulation of aldosterone secretion and its relationship to the pathogenesis of essential hypertension

The level of sodium intake has a reciprocal influence on the vascular and adrenal responses to angiotensin II, with sodium restriction enhancing the adrenal responses and reducing vascular, and particularly renal vascular, responses. In two subgroups of the essential hypertensive population, this relationship is abnormal. Both subgroups have sodium-sensitive hypertension. One is a subset of the low renin essential hypertensive subgroup and its abnormality is an enhanced aldosterone response to angiotensin II with sodium loading, ie, a failure to down-regulate the aldosterone response. The other subgroup, termed nonmodulators, is a subset of the normal-high renin essential hypertensive subgroup. In these patients, sodium intake modifies either adrenal or vascular responses, including renal vascular responses, to angiotensin II--resulting in a reduced aldosterone response to angiotensin II with sodium restriction. Of clinical importance, the nonmodulator's abnormality is corrected by the administration of converting enzyme inhibitors--this class of drugs therefore being a specific form of therapy in these patients.     

Hypertension Due to a Renin-Secreting Tumour Localised by Segmental Renal Vein Sampling

An 18-year-old female was found to be hypertensive on routine medical examination. Further investigation disclosed persistent hypokalaemia and elevated plasma renin activity in peripheral venous blood. Segmental renal vein sampling with assay of blood samples located the source of excess renin secretion in the lower mid-zone of the left kidney. This localization was not confirmed by either angiography or by palpation of the exposed kidney before nephrectomy but macroscopic examination of the freshly sectioned kidney revealed a small tumour in the region suggested by renal vein sampling. The tumour had the morphologic pattern of an haemangiopericytoma with abundant ultrastructural specific granules and very high renin activity by tissue assay. Plasma renin activity fell precipitously after nephrectomy and remained very low for the first week. Although the immediate post-operative blood pressure fell to normal, hypertension recurred temporarily and was associated with elevated plasma aldosterone, producing a syndrome similar to primary aldosteronism. All variables returned to normal without specific therapy and hypertension has not subsequently recurred.     

Importance of atrial natriuretic hormone in an exaggerated natriuresis during acute sodium load in primary aldosteronism.

To elucidate the factors which contribute to the exaggerated natriuresis in primary aldosteronism, hemodynamic and hormonal changes induced by saline infusion (at a rate of 0.5 l/h for 3 h) were examined in 6 patients with primary aldosteronism, 13 with essential hypertension, and 8 normotensive subjects. After saline infusion, increases in urinary sodium excretion, glomerular filtration rate, atrial natriuretic hormone, and urinary dopamine excretion along with suppression of plasma renin activity and aldosterone were compared in the three groups. All three groups demonstrated similar increases in glomerular filtration rate, but patients with primary aldosteronism did not show changes in urinary dopamine excretion, plasma renin activity, and aldosterone, despite their increased excretion of sodium. The increase in plasma atrial natriuretic hormone was significantly greater in primary aldosteronism than in essential hypertension or normotensive subjects. No changes in blood pressure or heart rate were seen. These findings suggest that atrial natriuretic hormone might play a role in the exaggerated excretion of sodium in patients with primary aldosteronism.     

Cytosolic free calcium concentration in platelets in patients with renovascular hypertension and primary aldosteronism.

To investigate the role of cytosolic free calcium, [Ca2+]i, in secondary hypertension, the levels in platelets from 14 secondary hypertensives (7 renovascular hypertension, 7 primary aldosteronism) were compared with those from 21 essential hypertensives and 15 normotensives by means of the fluorescent indicator, quin-2. The mean BP was significantly higher in both the secondary hypertensives and essential hypertensives (122 +/- 8 and 124 +/- 12 mmHg) than in the normotensives (89 +/- 10 mmHg). Cytosolic free calcium in platelets was significantly higher in the essential hypertensives, but not in the secondary hypertensives, compared with the normotensives (182 +/- 34, 141 +/- 17, 138 +/- 15 nM respectively). There was no significant difference in platelet [Ca2+]i between renovascular hypertension and aldosteronism (142 +/- 19 versus 139 +/- 16 nM). There was no correlation between platelet [Ca2+]i and plasma renin activity, plasma aldosterone concentration or plasma noradrenaline concentration in the three groups. Thus, the increase in platelet [Ca2+]i seen in essential hypertension was not found in patients with secondary hypertension. Our results suggest that the cytosolic calcium handling of secondary hypertensive patients with renal artery stenosis or primary aldosteronism differs from that of essential hypertensives.     

−344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension

Most patients with low renin essential hypertension are not qualitatively different from patients with idiopathic hyperaldosteronism, as in both conditions aldosterone secretion is not appropriately reduced. The aim of the study was to investigate allele and genotype frequencies of the −344C/T polymorphism, located in the promoter region of the aldosterone synthase gene, in 83 patients with idiopathic low renin hypertension characterized by an increased aldosterone to renin ratio, including both patients with low renin essential hypertension (n = 53) and subjects with idiopathic hyperaldosteronism (n = 30), compared with 78 patients with normal to high renin essential hypertension and 126 normotensive control subjects. The relationship of −344C/T genotypes to basal and post-captopril plasma aldosterone/plasma renin activity ratio was also examined in the entire hypertensive population. An increased frequency of the T allele and a relative excess of TT homozygosity over CC homozygosity were found in patients with idiopathic low renin hypertension in comparison with both normal to high renin hypertensives and normotensive controls. A higher post-captopril aldosterone to renin ratio was found in the hypertensives with TT genotype than in those with CC genotype, and TT+TC genotypes were associated with a smaller decrease in the aldosterone-to-renin ratio elicited by captopril administration. The present study suggests that the −344C/T polymorphism, or a functional variant in linkage disequilibrium with it, may play a role in the abnormal regulation of aldosterone secretion in idiopathic low renin hypertension.     

Outpatient Screening Tests for Primary Aldosteronism

Summary: Outpatient screening tests for primary aldosteronism. P. J. Dunn and E. A. Espiner, Aust. N.Z. J. Med. , 1976, 6 , pp. 131–135.
The assessment of basal plasma aldosterone and renin concentrations, and urinary aldosterone excretion has been compared with their values after a suppressive test employing mineralocorticoid induced volume expansion in five patients with primary aldosteronism and in patients with essential hypertension. Reliance upon measurements of basal plasma aldosterone concentration, plasma renin/aldosterone ratio and urine aldosterone excretion alone proved unsatisfactory for distinguishing patients with primary aldosteronism. However these patients, in contrast to those with essential hypertension, showed elevated values or no decrease in plasma aldosterone concentration following three days treatment with 400 μg fludrocortisone (florinef) daily. It is proposed that the assessment of basal plasma renin activity together with florinef suppression of plasma aldosterone are the most effective and convenient outpatient screening procedures in the diagnosis of primary aldosteronism.     

Endothelin-aldosterone interaction and proteinuria in low-renin hypertension

OBJECTIVE: To investigate whether endothelin and aldosterone participate in the increased prevalence and severity of nephrosclerosis in human low-renin hypertension, analogous to observations in experimental hypertension. DESIGN: Comparison of endothelin, aldosterone and their relationships with proteinuria, in hypertensive patients with high aldosterone : renin ratios (HARR group, n = 14) or normal aldosterone : renin ratios (NARR group, n = 15). METHODS: Urine protein and radioimmunoassay measurements of plasma renin activity, endothelin and aldosterone were carried out in individuals taking their usual diet, and after salt loading and salt depletion. RESULTS: Compared with the NARR group, patients in the HARR group had higher blood pressure, greater salt sensitivity of their blood pressure, significantly greater urine protein and lower serum potassium concentrations, lower renin activities [0.14 +/- 0.03 ng AngiotensinI (AI)/l per s compared with 0.76 +/- 0.16 ng AI/l per s; P < 0.005], blunted renin-aldosterone responses to salt loading and salt depletion, enhanced catecholamine responses to salt depletion, and increased plasma endothelin (5.1 +/- 0.5 fmol/ml compared with 3.7 +/- 0.3 fmol/ml; P < 0.03). In the HARR group, endothelin and aldosterone concentrations were highly correlated, and both correlated with blood pressure and urine protein. In contrast, in the NARR group, endothelin and aldosterone did not correlate between them or with blood pressure, and only endothelin, not aldosterone, correlated with urine protein. Multivariate regression confirmed that the interaction between aldosterone and endothelin was the major predictor of urine protein in the HARR group (r = 0.442), whereas endothelin, renin and their interaction were predictors in the NARR group (r = 0.467). CONCLUSIONS: Our results concur with experimental evidence for participation of endothelin in renal damage of angiotensin-dependent hypertension and for that of an endothelin-aldosterone interaction in low-renin hypertension. We propose that combined pharmacological antagonism of endothelin and aldosterone may confer renal protection beyond blood pressure reduction in patients with low-renin hypertension, a population at high risk for hypertensive nephrosclerosis.     

Obesity and the diagnostic accuracy for primary aldosteronism

The effects of body mass index on the diagnostic accuracy of primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co‐occurrence of obesity and hypertension. The current study included 59 adult patients who underwent a stepwise evaluation for PA, using aldosterone to renin ratio for case detection and plasma aldosterone concentration after saline suppression test and/or 24‐hour urinary aldosterone after oral sodium loading for case confirmation. Body mass index had a quadratic (U‐shaped) correlation with plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, and plasma aldosterone concentration after saline suppression test. Among patients with a body mass index ≥30 kg/m², the aldosterone to renin ratio yielded lower case detection accuracy of PA. We conclude that obesity results in a nonlinear correlation with plasma aldosterone concentration, plasma renin activity, and aldosterone to renin ratio, which affects the accuracy of case detection for PA. Patients with a body mass index ≥30 kg/m² are less accurately identified as having PA when saline suppression and/or oral salt loading tests are used for case confirmation.     

Aldosterone,Sodium and Potassium in Essential Hypertension

Eighty-five patients with essential hypertension received a restricted sodium diet for 10 days. During the last 5 days sodium intake was increased by oral administration of an additional 300 mmol of NaCl. At the end of both periods blood pressure, plasma and urinary concentration of Na and K, and 24–hour secretion rate of aldosterone (ASR) were determined. ASR in the hypertensives was after NaCl loading slightly higher than that in 21 normotensive controls. Aldosterone secretion rates were highest in patients with the lowest plasma K levels after loading with NaCl. This relationship between ASR and potassium was not found after NaCl restriction. After both NaCl restriction and NaCl loading the plasma K concentrations were lowest in patients with the highest mean arterial pressures. From statistical analysis of the relations between plasma Na, plasma K, ASR and mean arterial pressure it seems highly unlikely that aldosterone plays a prime role in the relation between the height of the blood pressure and the concentration of plasma K in essential hypertension. Our data seem in line with the presence of a primary abnormality in electrolyte metabolism in essential hypertension and slight aldosteronism after salt loading as its sequela.