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1. Riboflavin analogues were tested in three hypertensive rat models: the DOCA-salt hypertensive rat, spontaneously hypertensive rats (SHR) and Dahl S rats. 2. When 1.6 mg of 7,8-dimethyl-10-formyl-methylisoalloxazine (FMI) or 7,8-dimethyl-10-(2′-hydroxyethyl)isoalloxazine (HEI) was administered with 3.0 mg of DOCA twice weekly for 9 weeks, the systolic blood pressure (SBP) of the unanaesthetized rats rose to only 136 ± 5 mmHg compared with 165 ± 5 mmHg during DOCA treatment alone. The analogues blunted the retention of iliopsoas muscle Na+ and water due to DOCA. 3. In subsequent studies, the more potent riboflavin analogue 7,8-dimethyl-10-(3-chlorobenzyl)isoalloxazine (CBI) was employed. Administration of 0.5 mg of CBI/100 g body wt. twice weekly for 7 weeks lowered the SBP of the unanaesthetized SHR from 188 ± 7 mmHg to 148 ± 2 mmHg. The rats tolerated the medication well. CBI was more effective than hydrochlorothiazide, which at 2.2 mg/100 g body wt. daily only lowered the SBP to 167 ± 5 mmHg. The combined administration of CBI and hydrochlorothiazide produced an additive effect in that the SBP was reduced to 126 ± 4 mmHg. 4. CBI treatment resulted in a 36% and 11% decrease in the iliopsoas muscle Na+ concentration and water content respectively, suggesting that the untreated SHR is retaining Na+. The hydrochlorothiazide-treated SHR exhibited elevated levels of serum aldosterone. There was a profound suppressive effect of CBI on the secondary hyperaldosteronism generated by hydrochlorothiazide which was also reflected in the iliopsoas muscle K+ concentration. 5. In contrast to the SHR, the administration to the Dahl S rats of CBI for 8 weeks at 0.5 mg/100 g body wt. twice weekly reduced neither their SBP nor their iliopsoas muscle Na+ and water contents. 6. These results are consistent with our hypothesis that the antihypertensive actions of the riboflavin analogues are closely associated with their ability to modify the effects of mineralocorticoids on Na+ balance. These data suggest that riboflavin analogues also decrease aldosterone production and may function as dual-mechanism diuretic agents with K+ sparing properties and thus act as a novel class of antihypertensive drugs.

A simplified direct radioimmunoassay system for serum aldosterone measurement was developed by using radio iodine-labeled aldosterone and highly specific antiserum to aldosterone. 8-anilino-1-naphthalene sulfonic acid(ANS) was used to prevent the binding of aldosterone to serum proteins. Polyethylene glycol was used to separate the antibody-bound aldosterone from the free aldosterone as the precipitant. The minimum measurable concentration of aldosterone is 30pg/ml of serum by short incubation method (at 25 degrees C for 3hr incubation) and 15pg/ml of serum by long incubation method (at 4 degrees C for 20 hr incubation) respectively. Present radioimmunoassay eliminates extraction of the aldosterone from serum and chromatographic separation procedures, and requires only 0.1ml of serum sample for assay. The intra-assay precision was C. V. 6.9% (average of 4 samples) and the inter-assay precision was C. V. 10.7% (average of 4 samples). There is an excellent correlation between the extraction method and this direct method in serum aldosterone value obtained (correlation coefficient, 0.96). The normal value was 36.8+/-25.9pg/ml (recumbent) and 113.6+/-6.15pg/ml (upright).

SUMMARY We report two children of a family with congenital adrenocortical unresponsiveness to ACTH. Repeated stimulation of the adrenal by Synthetic 1–24 ACTH (Synacthen) failed to increase cortisol secretion, but produced significant rises of serum aldosterone. This was, however, associated with increased plasma renin activity. Only when the renin-angiotensin effect was eliminated, by a converting enzyme blocker, did Synacthen fail to affect serum aldosterone. These data support the view that glucocorticoid deficiency in this disorder results from unresponsiveness to ACTH and that development of the zona glomerulosa and normal aldosterone secretion is achieved by action of the renin-angiotensin system.

The effects of pulsatile cardiopulmonary bypass on the renin-angiotensin-aldosterone system and tissue metabolism, especially those which occur soon after surgery, were studied in 26 patients who required total cardiopulmonary bypass for longer than 60 minutes. These patients comprised 11 who underwent open heart surgery utilizing nonpulsatile cardiopulmonary bypass (Group I) and 15 who underwent open heart surgery utilizing pulsatile cardiopulmonary bypass (Group II). Plasma angiotensin II and serum aldosterone levels were significantly increased one and 5 hours postoperatively in Group I when compared with the preoperative values, whereas no significant elevations were observed in Group II. Plasma angiotensin II and serum aldosterone levels one hour postoperatively in Group II were significantly lower than those in Group I. Lactate levels in the arterial blood were significantly elevated, one and 5 hours postoperatively in both Groups I and II. Moreover, no significant difference was observed in the lactate levels between Groups I and II, one hour postoperatively. In the nonpulsatile group (Group I), plasma angiotensin II levels one hour postoperatively were correlated significantly with the duration of total cardiopulmonary bypass. In conclusion, pulsatile cardiopulmonary bypass offers significant advantages in terms of lower plasma angiotensin II and serum aldosterone levels, when compared with nonpulsatile cardiopulmonary bypass soon after open heart surgery requiring total cardiopulmonary bypass for longer than 60 minutes, however, it does not offer a definite advantage for tissue metabolism.

Beta-receptor agonist (terbutalin or isoxsuprin) administration to pregnant women either because of premature labor (therapy group; T; n = 8) or as prophylactic treatment (prophylaxis group; p; n = 8) resulted in a marked drop in serum potassium (p less than 0.001) during the first two hours of infusion in all patients. In five diabetic women in the P group the prolactin was significantly decreased (P less than 0.01) as was serum aldosterone levels (p less than 0.01). These changes were not observed in the T group. The two groups of pregnant women responded with a significant increase in free fatty acids (FFA) and glucose but the magnitude and the time coarse differed. Thus in T women, FFA reached a peak after 30-60 minutes into treatment and then returned to baseline levels. A closer analysis revealed that this pattern was only obtained in patients receiving terbutalin. Among women given prophylactic treatment with terbutalin, a continuous increase in FFA was noted over the initial two hours (p less than 0.001). The increase in serum glucose was continuous in the two patient groups (p less than 0.001). It is suggested that beta-receptor agonists in diabetic women induces a dopaminergic type of response since serum prolactin levels but not TSH concentrations were affected. The possibility that an increased PGE2 synthesis at the expense of PGF2 alpha might mediate this effect of beta-receptor agonists in discussed. It is also suggested that an increased prostaglandin synthesis might interfere with aldosterone secretion. The possibility that falling serum potassium levels may activate dopaminergic systems via PGE2 synthesis is also emphasized.

Two commercially available radioimmunoassay kits for aldosterone determination not requiring preliminary chromatographic purification were examined. Aldosterone standard curve solutions prepared from the CIS kit, Nuclear International Corp., (x-axis) and Diagnostic Products kit (y-axis) were assayed with both kits and the results yielded a regression equation of y = 0.834x + 0.08 nmol/liter. Analytical recovery experiments with aldosterone added to urine and serum showed 120% and 101% recovery with the CIS kit, respectively, and 92% and 92% recovery with the Diagnostic Products kit, respectively. Both kits demonstrated good parallelism with urine and serum. Antibody specificity was tested with six structurally related steroids and each kit showed virtually no cross-reactivity at clinically normal serum concentrations. Serum aldosterone values were compared before (y-axis) and after (x-axis) column chromatography on Sephadex LH-20, with the following regression equations: y = 1.070x + 0.092 nmol/liter for the CIS kit and y = 1.023x + 0.093 nmol/liter for the Diagnostic Products kit. Regression equations comparing patient samples between kits, CIS (x-axis) and Diagnostic Products (y-axis), were: y = 0.832x + 0.007 mumol/24 h with urine and y = 0.850x + 0.097 nmol/liter with serum.

Rats were fed 47 (deficient) and 606 ppm (adequate) magnesium with either 2,100 or 14,000 ppm sodium. Serum corticosterone and aldosterone levels were determined by randoimmunoassay in six rats from each treatment group killed on days 7, 14, and 28 of consumption of the experimental diets. Serum corticosterone levels were moderately, but not significantly, decreased in magnesium deficient animals. Serum aldosterone levels increased over time in the rats fed the lower sodium diet with adequate magnesium and were further elevated in magnesium deficient animals. In sodium loaded rats the increase in aldosterone levels in magnesium deficiency was less and occurred later. Retention and urinary excretion of sodium and potassium did not appear to be affected by magnesium status or the serum concentration of aldosterone. Possible mechanisms underlying the changes in aldosterone levels of magnesium depleted animals are discussed with reference to the known effects of magnesium deficiency on physiological functions.

Xenopus laevis adult females exposed to progressive water deprivation and maintained under dry conditions for two weeks showed a statistically significant increase in serum aldosterone and cortico‐sterone levels in response to osmotic stress. These results are in accordance with those previously obtained by us in males from this typically aquatic species subjected to the same experimental conditions. In females returned to water for one week after a two week period of dehydration, serum aldosterone and corticosterone returned to values approximating those of control.

Summary The specific activity of mucosal Na-K-ATPase in segments of the small intestine and colon was examined after bilateral nephrectomies (BN), bilateral upper ureteral ligations (BUUL) and bilateral lower ureteral ligations (BLUL). Animals were studied 22–26 h after these respective operations. Bilateral nephrectomies and bilateral upper ureteral ligations resulted in an increase of the specific activity of the enzyme throughout the mucosa of the intestinal tract. Bilateral lower ureteral ligations induced no significant change in the specific activity of Na-K-ATPase in the intestinal mucosa. There were no differences in the degree of renal failure. Marked aldosteronemia was observed in the BN and the BUUL rats but not in the BLUL rats. These data suggest that the increase in the intestinal Na-K-ATPase activity in the BN and the BUUL rats may be related to the elevation of serum aldosterone as a regulator of the body potassium.

Serum aldosterone values were determined in 6 elderly (70-82 years) and in 6 adult (31-43 years) male subjects after the intravenous administration of 10 mg of metoclopramide. A significant difference in the metoclopramide-induced serum aldosterone rise was found between the two groups, it being blunted in the older subjects (serum aldosterone peak values: 15.8 +/- 3.6 ng/dl and 38.7 +/- 4.9 ng/dl in elderly and in adult subjects, respectively). The existence of an impaired aldosterone secretion in response to dopaminergic blockade in the elderly is postulated.

A shortened, simplified radioimmunoassay for serum aldosterone has been made possible by the development of a highly specific antiserum for aldosterone. This high specificity is largely due to the careful purification of the aldosterone-3-oxime derivative. Using 50% displacement of 1,2-3H-aldosterone as a measure, no other steroid cross-reacts to a degree greater than 0.015% (18-OH-DOC) and most cross-react less than 0.00003%. Recovery, accuracy and sensitivity are quite satisfactory using only serum extraction with methylene chloride and no further separation. The normal range found is comparable with others reported (3–35 ng/100 ml) although women are shown to have more variable levels than men.

1. Deoxycorticosterone acetate (DOCA) implantation (100 mg/kg) caused mean arterial pressure to rise in 5–10 days from control pressures of 100–115 mmHg to stable hypertensive valnes of 140–160 mmHg in approximately 1 month. In six of seven pigs elevations of mean arterial pressure were entirely the result of increased total peripheral resistance. 2. Single implants maintained serum DOCA at approximately ten times normal concentration for up to 90 days. 3. Moderate but variable decreases in serum aldosterone followed implantation. 4. Hypokalaemia, polydipsia and suppressed plasma renin activity were evident by the fifth post-implantation day and persisted thereafter. No consistent change occurred in serum sodium. 5. Noradrenaline or angiotensin caused increases in total peripheral resistance at lower threshold infusion rates in hypertensive pigs compared with control animals. 6. In isolated, perfused hind-limb preparations, hypertensive vascular beds were characterized by both functional (increased vascular smooth muscle sensitivity) and structural (elevated resistance of maximally dilated vascular bed) changes. ‘Protection’ from increased arterial wall stresses in hypertensive pigs prevented structural, but not functional, alterations.

SUMMARY The effect of L-dopa (0·50 g, orally) on serum aldosterone, cortisol and potassium levels, plasma renin activity, and on urinary aldosterone excretion has been studied in normotensive subjects, before and after dexamethasone-induced ACTH suppression. L-dopa caused a further reduction in the levels of aldosterone but not cortisol, in the dexamethasone treated subjects. It is therefore suggested that the inhibitory action of L-dopa on aldosterone secretion is mediated by the dopaminergic system.

Previous studies have shown that increased sodium chloride in drinking water failed to suppress serum renin activity (SRA) in the ether-anesthetized rat. In the absence of anesthesia, sodium chloride decreased SRA by 76%SS and serum aldosterone by 72%. Deoxycorticosterone acetate, when given alone, produced similar results but was more effective in reducing SRA (96%) when com-bined with sodium chloride. However, if “light” ether anesthesia was administered prior to blood collection, there was a 10-fold increase in SRA and the effects of sodium chloride were blocked. Thus, n i the absence of anesthesia, the renin-angiotensin-aldosterone system of the rat responds, as in other species, to a sodium load.(Endocrinology 97: 1394, 1975)

Two antibody method of aldosterone RIA kit was investigated. This kit was measured directly without extracting the aldosterone. On fundamental studies, stability of standard curve, reproductivity, recovery test and dilution test were obtained good results. On clinical studies, the diurnal variation of serum aldosterone concentration in normal child and adult was correlated well to that of concentration of cortisol and ACTH. The concentration of three hormones was the highest in the early morning and it was the lowest in midnight.

Nine 20- to 26-year-old and ten 70- to 78-year-old diurnally active, nocturnally resting women in Wurzburg, Federal Republic of Germany, gave blood at 0700, 1000, 1300, 1600, 1900, and 2200 for radioimmunoassay of aldosterone. Single and population-mean cosinors were applied. A multivariate analysis of circadian rhythm characteristics revealed effects of age on the amplitude (p = .003) but not the mesor of aldosterone in women (i.e., the age effect could only be detected at certain circadian times but not at others). No change with age was found for concomitantly sampled men. Statistically significant interactions among circadian time, age, and sex (p = .001) establish the adrenocorticopause in women and suggest that it may occur earlier in women than in men, in keeping with similar results on serum cortisol in the same subjects. This phenomenon awaits scrutiny from the viewpoint of its bearing on longevity and life quality. These results also indicate the importance of assessing chronobiological characteristics.

Because of the atypical symptomatology, which can mimic an EPH-gestosis, the physiological elevation of serum aldosterone in the third trimester and restricted diagnostic possibilities, the diagnosis of primary hyperaldosteronism during pregnancy is difficult. A case of an adrenal adenoma during pregnancy is reported.