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1. The determination of aldosterone-18-glucuronide (pH 1-labile aldosterone) was complemented by concomitant measurements of free urinary aldosterone and tetrahydroaldosterone in 307 patients, most of whom were hypertensive. In 38 cases (12·3%) the normal, aldosterone-18-glucuronide concentration was clinically misleading, but increased free aldosterone and/or tetrahydroaldosterone values suggested the presence of hyperaldosteronism, which in many of these cases was confirmed by elevated excretion of the possible major aldosterone precursor 18-hydroxycorticosterone (18-OH-B). 2. Of 224 patients with essential hypertension and normal or low plasma renin activity 18 had an elevated free aldosterone and/or tetrahydroaldosterone excretion without increased aldosterone-18-glucuronide. These cases may represent early or pre-symptomatic forms of primary hyperaldosteronism. In other cases, particularly when tetrahydroaldosterone was increased alone, abnormalities of aldosterone metabolism were suspected. 3. In two out of 15 patients with primary hyperaldosteronism, aldosterone-18-glucuronide values were frequently found to be normal, although elevations were noted in other variables. However, no relation to the morphological abnormality (adenoma versus hyperplasia) was seen.

Antisera against tetrahydrocorticosterone (THB) (one of the metabolites of the glucocorticoid corticosterone) were raised in white New Zealand rabbits. A 3α,5β-THB-20-oxime-bovine serum albumin complex was used as antigen. The resulting titers were 1/300–1/19 000. The cross-reactions of the best antiserum were: THDOC 2.25%, THB-21-glucuronide 39%, and THF-21-glucuronide 4.8%. Other steroids and steroid metabolites have given negligible cross-reactions, e. g. allo-(3α,5α-)-THB 0.53 %, tetrahydro-11-dehydro-corticosterone (THA) 0.92%, allo-THA 0%, and THB-3-glucuronide 0 %.Two methods were introduced: a) for screening an estimation of THB-glucuronide, mostly THB-21-glucuronide ("THB-gluc."), in unprocessed urine after simple dilution b) specific estimation of THB using one paper chromatographic system.The values estimated by method a) showed a highly significant correlation (r = 0.9654, P< 0.01) with the values obtained by technique b).Normal values (method b) measured in subjects hospitalized under standardized conditions were: 21.8–177.6; mean 89.1 μg/24 h.THB levels and "THB-gluc." levels react to ACTH stimulation and dexamethasone suppression and thus we propose that the methods are useful for the diagnosis of hyper- and hypocorticosterone production states.

To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR-SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake.

The development of hypertension, which had been elicited by clamping one renal artery in the presence of an untouched contralateral kidney, has been pursued in rats for up to six weeks after operation, and aldosterone and corticosterone production was studied at various intervals.Two weeks after renal artery stenosis had been induced, a "benign" and a "malignant" course of hypertension could be distinguished, the latter being characterized by a rise in blood pressure beyond 180–190 mmHg, loss of salt and water, increased water intake, decrease in body weight and food intake, and stimulation of the renin-angiotensin system.In the early phase of hypertension (after 9 days), aldosterone production and plasma aldosterone concentration were already elevated, and so was plasma corticosterone concentration. After 16 days, a marked increase in aldosterone production and in both plasma aldosterone and corticosterone concentrations was obtained in malignant hypertensive rats, whereas the secretion of the two hormones was only slightly stimulated in benign hypertensive rats. Similar differences in aldosterone production between rats with benign or malignant hypertension were found 21 and 42 days after operation.After 21 days, a close relationship between plasma renin concentration and aldosterone production was obtained in malignant hypertensive and control rats. A positive correlation between plasma concentrations of angiotensin II and of aldosterone was calculated for rats with malignant hypertension.It is concluded that, in the malignant phase of renal hypertension, a state of secondary aldosteronism develops as a consequence of negative sodium and water balance induced by high blood pressure.

Zusammenfassung Ein verbesserter Test zur Diagnose Renin-abhängiger Bluthochdruckformen mit dem Angiotensin II Rezeptor Antagonisten Saralasin wurde in hypertensiven Ratten, sowie in normotensiven und hypertensiven Patienten geprüft. Kumulative intravenöse Dosen, beginnend mit 0,01 µg/kg × min Saralasin wurde alle 15 Minuten um das zehnfache gesteigert. Ein signifikanter Blutdruckabfall bei der Dosis von 0,1 µg/kg × min wurde bei Ratten mit renaler Hypertonie, bei Patienten mit renaler Hypertonie und bei Patienten nach Diuretika-Vorbehandlung gefunden. Plasmaspiegel von Angiotensin I, Angiotensin II, Plasma Renin Aktivität und Saralasin wurden gemessen. Bei der niedrigsten Infusionsrate von 0,01 µg/kg × min waren die Saralasin-Konzentrationen im Plasma 40fach höher als die Plasma Angiotensin II-Konzentrationen. Der Blutdruckabfall erfolgte bei niedrigeren Dosen von Saralasin als der Anstieg von Plasma-Renin als Folge einer Hemmung des feedbacks der Reninsekretion.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar–Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin–angiotensin–aldosterone system and 18-hydroxy-deoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower Pco2 and HCO−3 values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

In rabbits immunized with hemisuccinate-albumin complexes of cortisol, corticosterone, deoxycorticosterone, and aldosterone, or against all 4 corticoids simultaneously, antibody titres and plasma concentrations of the corresponding hormones were measured by means of radioimmunoassay.In immunized rabbits, plasma concentrations were generally higher than in non-immunized controls. Plasma concentrations of cortisol were above 100 μg/100 ml in the animals with the highest cortisol antibody titres (control below 3.5 μg/100 ml). Plasma corticosterone concentrations reached levels of 20–100 μg/100 ml (control below 3.5 μg/100 ml) in rabbits immunized against corticosterone, deoxycorticosterone, or against all 4 corticoids. Concentrations of aldosterone in rabbits immunized against this hormone were 100–1000 times higher than in the control animals (17.9 ± 3.4 ng/100 ml). In all immunized animals the disappearance of intravenously administered labelled corticoids from plasma was delayed as compared with controls, indicating a diminished plasma clearance rate. After administration of ACTH, plasma concentrations of cortisol and corticosterone were the more elevated, the higher the antibody titre was.Despite the high antibody titres, immunized animals had no signs of adrenal insufficiency. On the contrary, some of the animals showed symptoms of hypercorticism.The mechanisms that may be responsible for the elevated plasma concentrations of the various corticoids are discussed.

Aldosterone antibodies were raised in sheep immunized with a complex of D-aldosterone-21-hemisuccinate and bovine serum albumin. The intravenous injection of these antibodies into rats caused a delay in the disappearance rate of tritiated aldosterone from the blood. The degree of this effect depends on the body weight of the animals, on the amount of the antiserum given, and on the interval between the injection of antibodies and that of labelled aldosterone.After the injection of aldosterone antibodies and the tritiated hormone, the plasma concentration of labelled aldosterone was related to the rate of secretion of the hormone. When aldosterone secretion was low, subsequent to high sodium intake, or abolished after adrenalectomy, the plasma concentration of tritiated aldosterone was higher than in the control rats. Stimulation of aldosterone secretion by furosemide or ACTH, or administration of cold aldosterone resulted in a decrease in the plasma concentration of the labelled hormone. It is suggested that the relationship between the amount of free aldosterone in the "inner pool" and the plasma concentration of tritiated aldosterone is the consequence of a competition of labelled and unlabelled hormone for the binding capacity of the antibody.