Increase In Aldosterone Excretion Research Articles

Calcineurin-NFATc4 Pathway Is Activated Upon K+-stimulation of Adrenal Aldosterone Production

The mineralocorticoid aldosterone secreted by the adrenal zona glomerulosa (ZG) cells promote renal K+ secretion and Na+ reabsorption; thereby it is critical for the control of ion homeostasis and blood pressure. While the Ca2+/calmodulin-dependent protein kinase (CAMK) pathway regulating K+ stimulated aldosterone production is well studied, little is known about the potentially involved phosphatases. Interestingly, immunosuppression therapy of transplanted patients with protein phosphatase 3 (calcineurin) inhibitors often results in rather low plasma aldosterone levels despite a concomitant hyperkalemia and hyperreninemia. Calcineurin (Cn) is a calcium and calmodulin-dependent protein phosphatase expressed in the adrenal cortex. We tested the hypothesis that Cn participates in the signal transduction pathway mediating the K+-dependent stimulation of aldosterone production. To address this question, we used the adrenocortical cell model NCI-H295R, mouse and human ex vivo adrenal preparations and a ZG-specific and inducible Cn knockout mouse model (ZG-CnB1-KO). Inhibition of Cn with tacrolimus abolished the K+-stimulated expression of CYP11B2 in NCI-H295R cell line as well as mouse and human adrenal pieces, ex vivo. Using a phosphoproteomics analysis, we identified nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4) as a critical downstream factor mediating Cn function. In support of this result, genetic deletion of NFATc4 reduced the basal expression of CYP11B2 and impaired the K+-stimulated expression of this gene. Conversely, the expression of a constitutively active form of NFATc4 drastically increased the expression of CYP11B2 in NCI-H295R cells which remained unaltered upon treatment with K+ or tacrolimus. Finally, preliminary experiments using ZG-CnB1-KO mice suggest that Cn deletion in the ZG blunts the increase in aldosterone excretion triggered by high K+ diet. Altogether, our data indicate that Cn function is indispensable for the physiological regulation of aldosterone production. Moreover, Cn may represent a novel molecular target for the pharmacological treatment of primary aldosteronism.

SAT-LB301 Hyperaldosteronism From Adrenal Adenoma in a Young Patient

Introduction Primary aldosteronism (PA) is the most common cause of secondary hypertension (HTN) that is often underdiagnosed. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex- matched patients with essential HTN and the same degree of blood pressure elevation. We present a case of a 17-year old male with primary hyperaldosteronism. Case Report 17-year-old male with no past medical history presented to the emergency department referring bitemporal cephalea, pain in left arm, dyspnea, heart palpitations, a blood pressure (BP) of 220/110 mmHg and a serum potassium of 1.5mmol/L (n. 3.5-5). The patient was admitted to the hospital for better handling of his BP, potassium repositions, monitoring and further management. During hospitalization he referred leg cramps, asthenia, adynamia, nausea, cephalea, and blurred vision. Physical examination demonstrated decreased muscle strength, jugular regurgitation II and hyperreflexia on lower extremities. Thyroid and pulmonary examinations were normal. BP continued elevated despite the concurrent use of 3 antihypertensive drug classes (ARA2, BB, CCB), referred to endocrinologist after being diagnosed with resistant hypertension suspecting of a primary hyperaldosteronism. Lab tests were run obtaining a plasma aldosterone concentration 44ng/dl (n. 4-31), plasma active renin (PRA) 0.05ng/ml/hr (n. 0.2-1.6), aldosterone/PAR ratio 880 (<25 normal). Suprarenal CT scan revealed right suprarenal lesion 2.2 x 2.1 cm, round appearance, hypodense (14 HU) compatible with an adenoma. He underwent unilateral adrenalectomy. Histopathological report from excised adrenal tumor was compatible with a benign adenoma. Patient was discharged with a regularized blood pressure without antihypertensives and normokalemic. No clinical symptoms were reported in follow-up. ConclusionPrimary aldosteronism (PA) is the most common form of secondary hypertension (HTN) with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. PA is characterized by hypertension, hypokalemia, suppressed plasma renin and increased aldosterone excretion. Aldosterone producing adenomas (APAS) account for around 40% and idiopathic hyperaldosteronism for around 60% of PA cases. The most sensitive screening test for PA is the aldosterone-to-renin ratio. After case confirmation, all patients with PA should undergo adrenal CT as the initial study. Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with APAs, and bilateral hyperplasia should be treated with mineralocorticoid antagonist.

Ventricular Arrhythmia and Left Ventricular Dysfunction: A Rare Manifestation of Adrenal Adenoma

Primary aldosteronism is characterized by hypertension, suppressed plasma renin activity, increased aldosterone excretion, and hypokalemia with metabolic alkalosis. Ventricular arrhythmia is an uncommon finding. We report the case of a 46-year-old female who was referred to our center due to uncontrolled ventricular arrhythmia. The past medical history was positive for hypertension. On admission, echocardiography showed severe left ventricular (LV) dysfunction. Blood examination revealed severe hypokalemia. She had been diagnosed with acute coronary syndrome and decompensated heart failure elsewhere and was given diuretics. A diagnosis of primary aldosteronism due to adrenal adenoma was made according to laboratory findings and imaging modalities. The prompt management of bradycardia and correction of hypokalemia, along with surgical resection of adrenal adenoma, resulted in control of arrhythmias and improvement in LV function.

Rhabdomyolysis due to primary hyperaldosteronism

Rhabdomyolysis may be secondary to trauma, excessive muscle activity, hereditary muscle enzyme defects and other medical causes. Primary hyperaldosteronism is characterised by hypertension, hypokalemia, suppressed plasma renin activity, and increased aldosterone excretion. Rhabdomyolysis is not common in primary hyperaldosteronism. We report here a 42-year-old woman presenting with rhabdomyolysis as heralding symptom of primary hyperaldosteronism. We also carried out a search of the literature to identify all cases of rhabdomyolysis as the first-recognized expression of a primary hyperaldosteronism. Sixteen cases met the criteria for inclusion. When rhabdomyolysis occurs in a patient with hypokalemia and metabolic alkalosis, primary hyperaldosteronism has to be suspected: if confirmed, an aldosterone-producing adenoma is the most probable cause.

Aldosterone Excretion Among Subjects With Resistant Hypertension and Symptoms of Sleep Apnea

The severity of obstructive sleep apnea (OSA) correlates with the difficulty of controlling BP. The mechanism, however, by which sleep apnea contributes to the development of resistant hypertension remains obscure. Having observed a high prevalence of OSA among hypertensive subjects with primary hyperaldosteronism, we hypothesized a possible association between sleep apnea and aldosterone excretion. In consecutive subjects referred to a university clinic for resistant hypertension, we prospectively determined plasma renin activity (PRA), plasma aldosterone concentration (PAC), and 24-h urinary aldosterone excretion during high dietary salt ingestion. In addition, all subjects completed the Berlin Questionnaire, a survey designed to identify subjects at risk of having sleep apnea. Primary hyperaldosteronism (PA) was defined as a PRA < 1.0 ng/mL/h and 24-h urinary aldosterone excretion > 12 micro g during high urinary sodium excretion (> 200 mEq/24 h). Of the 114 subjects evaluated, 72 subjects had a high probability and 42 subjects had a low probability of having sleep apnea based on their responses to the Berlin Questionnaire. Subjects at high risk for sleep apnea were almost two times more likely to have PA diagnosed (36 vs 19%, p < 0.05), tended to have lower PRA (1.2 +/- 1.8 ng/mL/h vs 1.9 +/- 4.1 ng/mL/h), and had significantly greater 24-h urinary aldosterone excretion (13.6 +/- 9.6 micro g vs 9.8 +/- 7.6 micro g, p < 0.05) compared to subjects at low risk of sleep apnea. These data provide evidence of increased aldosterone excretion in subjects with resistant hypertension and symptoms of sleep apnea. While the causality of this association is unknown, it is hypothesized that sleep apnea contributes to the development of resistant hypertension by stimulating aldosterone excretion.

The effects of VDT work on the regulation of hemodynamics compared with aging

Urinary excretions of aldosterone, blood pressure, and heart rate were examined for three age groups of volunteers searching for target words on VDT for two hours. Aldosterone excretion did not change in the young and middle-aged groups, but increased in the elderly group. Blood pressure decreased midway through the work in the young group, and increased during the work in the middle-aged and elderly groups. Aldosterone excretion did not increase during hard-copy work or during VDT work with large letters, but increased during VDT work with small letters. During VDT work with both large and small letters, blood pressure increased. During hard-copy work, neither blood pressure nor heart rate changed, although blood pressure increased after the work. These data suggest that the sympathetic nervous activation represented by the increases in aldosterone excretion and blood pressure occurred definitively during VDT work with small letters under the conditions of this study. It is also suggested that this effect is enhanced by aging.

Studies on Mechanisms of Antinephritic Action of SA-446, an Angiotensin I Converting Enzyme Inhibitor (1) A Comparison with Actions of Spironolactone, Kallidinogenase and Saralacin

The present study was made to clarify the mechanisms of the antinephritic action of SA-446, an angiotensin I converting enzyme inhibitor, on crescentic-type anti-GBM nephritis in rats as compared to the actions of spironolactone (an antialdosterone agent), kallidinogenase (a kallikrein agent) and saralasin (an angiotensin II antagonist). SA-446 (25 mg/kg/day, p.o.) had a tendency to reduce the urinary protein excretion and plasma urea nitrogen content. In addition, this drug remarkably inhibited not only glomerular histopathological changes (i.e., crescent formation, the adhesion of capillary walls to Bowman's capsule and fibrinoid necrosis) but also the elevation of blood pressure. Spironolactone (25 mg/kg/day, p.o.) and kallidinogenase (25 KU/day, i.m.) also showed beneficial effects on glomerular histopathological changes and hypertension, although both drugs were not as effective as SA-446. Flowever, saralasin (72 μg/day, s.c.) caused a marked aggravating action on this nephritis. This nephritic model showed a marked low activity of plasma renin all through the 40 day experimental period. In this model, the urinary aldosterone excretion was increased, in spite of the decrease in plasma renin activity. SA-446 and kallidinogenase significantly inhibited the decrease in plasma renin activity and the increase in urinary aldosterone excretion. Spironolactone inhibited only the increase in the aldosterone excretion. However, saralasin decreased the plasma renin activity under the control level and strongly increased the urinary aldosterone excretion (about 1.8 times the control level on the 20th day). These results suggest that the antinephritic effect of SA-446 may be related to the antihypertensive action and the increase in renal blood flow through activation of the kallikrein-kinin and prostaglandins systems.

Systemic and splanchnic hemodynamic disturbances in conscious rats with experimental liver cirrhosis without ascites.

Rats with CCl4-induced cirrhosis of the liver show histological and clinical features that closely resemble those of the disease in humans. Metabolic cages were used and hemodynamic studies (15-micrograms radioactive microspheres) were performed on 10 conscious, nonascitic, cirrhotic rats and in 10 control rats. Compared with control animals, cirrhotic rats showed lower sodium excretion (0.80 +/- 0.07 vs. 1.01 +/- 0.07 meq/day), total solute excretion (12.52 +/- 0.79 vs. 19.38 +/- 3.7 mosmol/day), and increased aldosterone excretion. No differences were observed in urinary epinephrine and norepinephrine excretion. Cirrhotic rats showed also slight hypotension, increased cardiac output (48.97 +/- 3.94 vs. 26.97 +/- 2.3 ml X min-1 X 100 g-1) without tachycardia, and decreased total peripheral resistance, which was mainly attributed to reduced renal and skeletal muscle resistances with increased blood flow throughout these areas. Cirrhotic rats showed increased hepatic vascular resistances by both portal and arterial inputs with portal hypertension (16.15 +/- 1.01 vs. 9.60 +/- 0.77 cmH2O) but without differences in total hepatic blood flow or portal-systemic shunt rate with respect to control rats. Plasma renin content was not significantly different between the groups of rats. From these data it can be concluded that nonascitic, cirrhotic rats show a hyperdynamic circulatory state, which seems to be caused by a peripheral vasodilation of unknown mechanism; portal-systemic shunting does not seem to be a necessary condition for the hyperdynamic status at this early stage of the hemodynamic disturbances.

Aldosterone escape to chronic ACTH administration in man.

Abstract. Prolonged ACTH administration produces a transient and self-limiting stimulation of aldosterone secretion which has been attributed to sodium retention, to inhibition of final enzymatic steps of aldosterone biosynthesis and/or to a morphological change of the glomerulosa cells. This study was undertaken to determine the possible role of the renin-angiotensin system in mediating the aldosterone escape to repeated ACTH stimulation. We studied in normal male volunteers the effect of a 4 day ACTH administration on urinary aldosterone metabolite excretion (3 oxo-conjugate and tetrahydroaldosterone) during concomitant diuretic administration (spironolactone or triamterene). In addition the plasma aldosterone response to acute iv stimulation with ACTH before and during the corticotrophin-induced 'refractory state' was examined both on normal and on low sodium diet. Spironolactone was unable to counteract the sodium retention induced by ACTH stimulation; aldosterone excretion showed the same transient increase as with ACTH alone while plasma renin activity remained low. Triamterene produced a negative sodium balance, a significantly more sustained increase in aldosterone excretion and an increase in plasma renin activity. In either situation the two metabolites of aldosterone showed the same pattern of excretion. The plasma aldosterone response to acute iv ACTH stimulation was completely blocked during the corticotrophin-induced 'refractory state' on normal sodium intake, whereas on low sodium diet a clear-cut response was still obtained. These data suggest that the transient effect of ACTH on aldosterone secretion is dependent on the state of activity of the renin-angiotensin system. When renin was stimulated by low sodium intake or sodium depletion, the aldosterone response to repeated ACTH administration was more sustained, and when renin was stimulated by low sodium intake, the aldosterone response to acute ACTH was maintained. In conclusion we suggest that the renin-angiotensin system is able to delay but not to suppress the changes induced in the zona glomerulosa by prolonged ACTH stimulation.

Effects of Nifedipine during Low, Normal and High Intakes of Sodium in Patients with Essential Hypertension

1. Nifedipine (20 mg) was given by mouth to seven patients with moderate essential hypertension receiving a low, normal or high sodium intake. The drug produced an important hypotensive effect. Normal sodium intake enhanced the hypotensive action of the drug compared with that during the low and high sodium regimens. Blood pressure remained significantly lower 3 h after drug ingestion. 2. Increases in heart rate and plasma renin activity under all conditions reflected enhanced adrenergic activity. 3. A short-term natriuresis followed nifedipine ingestion in spite of increased aldosterone excretion during the low sodium diet and a decrease in urinary kallikrein during the low and high sodium diets. 4. Nifedipine increased urinary volume only during the high sodium intake. 5. Apart from vasodilatation, nifedipine induces important changes in neurogenic, renal and adrenal mechanisms that regulate blood pressure homoeostasis. Different conditions of sodium balance modulate most of these effects.

THE EFFECT OF DIETARY SODIUM IN INFANCY ON BLOOD PRESSURE AND RELATED FACTORS: Studies of Infants Fed Salted and Unsalted Diets for Five Months at Eight Months and Eight Years of Age

The results of animal and epidemiological studies suggest commercially salted infant foods may predipose infants to hypertension. Testing this hypothesis, two groups of black male infants were fed identical foods with and without added salts for 5 months starting at 3 months of age. These diets, which provided 1.93+/-0.10 and 9.25+/-0.05 mEq Na/100 kcal, did not result in a significant difference in blood pressure at 8 months or 8 years of age. Blood pressure was significantly correlated with weight factors, particularly at 8 years, but not with Na intake, Na or Na/K excretion or plasma renin at 8 months. Significantly increased sodium and potassium excretion was noted on the salted diet and significantly increased aldosterone excretion was noted on the unsalted diet. A 6% expansion in extra-cellular fluid volume for the high sodium group was statistically significant but was not correlated with blood pressure or urine volume and did not result in edema or increased weight. There was no indication that the salted foods imprinted a preference for salt at 8 years. It was concluded that a salt intake representing the 99th percentile of sodium intake by U.S. infants in 1969 had no hypertensive effect in infancy or at 8 years of age. Nor did it imprint a preference for salt at 8 years.

Space motion sickness medications: Interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2–4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.

Disparate patterns of aldosterone response during diuretic treatment of hypertension.

In 50 patients with essential hypertension treated with chlorthalidone, 100 mg daily for 6 weeks, treatment responders (fall in mean pressure, greater than or equal to 10%) and nonresponders experienced similar weight and electrolyte changes. Although induced increments and post-treatment values of plasma renin were higher in nonresponders than responders, there was a far more striking difference in aldosterone reactivity. Aldosterone excretion rose by less than 10% in the responders but almost doubled in the nonresponders. Again, within the normal renin subgroup alone (n = 28), nonresponders exhibited control renin values and treatment-induced changes in plasma renin closely similar to those in responders, but experienced a significantly greater increase in aldosterone excretion. Possibly this increase in aldosterone produced subtle volume retention or a direct pressor effect in nonresponding patients. Although changes in aldosterone and in renin correlated with each other in both responders and nonresponders, the slopes of the regression lines in the two groups differed significantly. Thus, cofactors governing sensitivity of the aldosterone response to renin stimulation ultimately may determine the antihypertensive effectiveness of diuretics.

The Efficacy and Safety of Furosemide and a Combination of Spironolactone and Hydrochlorothiazide in Congestive Heart Failure

The therapeutic and biochemical effects of two commonly employed diuretic preparations were compared in a double-blind fashion in 32 patients with congestive heart failure. At the doses employed, furosemide and a fixed combination of spironolactone and hydrochlothiazide maintained control of the clinical manifestations of congestive heart failure to about the same degree. However, significant biochemical changes in the renin-aldosterone system were found in patients receiving the spironolactone/thiazide combination therapy. A significant increase in plasma renin activity and a significantly greater increase in aldosterone excretion were found in the spironolactone/thiazide group compared to the furosemide group. No significant differences were observed in serum potassium levels or 24-hour potassium excretion rates in patients treated with the two diuretic preparations.

STUDY ON ALDOSTERONE EXCRETION DURING PHENOBARBITAL NIKETHAMID PROPHYLAXIS OF HYPERBILIRUBINAEMIA

The investigation yielded the following results:1. In full term new-borns a significant increase in aldosterone excretion is observed on the 4th, 7th and 14th days of life as compared to the 1st day. The excretion does not decrease significantly on the subsequent days of examination.2. In new-borns treated with phenobarbital/nikethamid, an analogous increase of aldosterone took place duri during the first 14 days of life, the decrease after the 4th day of life being statistically significant in this group.3. Between both groups there are no differences in fluid and electrolyte excretion.4. Neither in treated nor in untreated children, a positive correlation between the amount of aldosterone secretion and the urine parameters under investigation could be observed.The evaluated results indicate that increased aldosterone excretion in the treated group is caused by the known increase of glucuronidizing activity due to phenobarbital/nikethamid.

Effect of aldosterone antagonist canrenone on plasma aldosterone concentration and plasma renin activity, and on the excretion of aldosterone and electrolytes by man.

Canrenone was administered in doses of 2 x 82 mg and 2 x 164 mg per day over a period of 10 days to diabetic patients without cardiovascular, liver or kidney involvement. Aldosterone excretion and plasma aldosterone increased only slightly during both regimes. There was a clear-cut increase in aldosterone excretion only after discontinuation of canrenone. Excretion of sodium, potassium and fluid was not significantly changed either during or after treatment. The lack of effect of canrenone on the kidney was in contrast to the significant decrease in serum sodium and increase in serum potassium, and the significant, dose-dependent rise in plasma renin activity following canrenone administration. The increased plasma renin activity persisted for some days after discontinuation of canrenone. It is suggested that canrenone primarily exerted its effect in the distal part of the large intestine where ionic movements are most affected by aldosterone. The disproportionately slight increase in plasma aldosterone concentration and aldosterone excretion, in spite of the greatly elevated plasma renin activity and serum potassium level, is considered to be due to a direct inhibitory effect of canrenone on aldosterone production in the adrenals.

The effect of saluretics and spironolactone on aldosterone production and electrolyte excretion in man.

Healthy volunteers received orally the saluretics furosemide (40 mg/day) and thiabutazide (10 mg/day) over a 5-day period, and the aldosterone antagonist spironolactone (5 mg and 10 mg/kg per day) over 7-and 3-day periods, respectively. On the first day of treatment both saluretics induced a marked increase in sodium and water excretion, but only a moderate increase in potassium excretion. On the second day, however, the sodium and water excretion had already returned to almost normal values, reaching a minimum after discontinuation of the saluretics. Under saluretic therapy, a steep increase in plasma aldosterone concentration and in urinary aldosterone was observed. After the saluretics were discontinued, both the markedly elevated plasma aldosterone concentration and the aldosterone excretion returned to normal within two days. Under saluretic therapy potassium excretion appeared to be aldosterone-dependent, since potassium excretion paralleled aldosterone excretion. Spironolactone (5 mg/kg oder a 7-day period) caused a moderate increase in sodium excretion and a moderate decrease in potassium excretion. Spironolactone (10 mg/kg over a 3-day period) caused a distinct increase in sodium excretion and a slight decrease in potassium excretion. Neither of the two spironolactone doses used here produced an increase in aldosterone excretion. After discontinuation of spironolactone, a rebound in aldosterone excretion was observed. The increase in aldosterone excretion was associated with corresponding changes in electrolyte excretion. The increase in aldosterone excretion and in plasma aldosterone concentration induced by the saluretic thiabutazide was markedly reduced by the administration of spironolactone (10 mg/kg). The sodium and water retention which was caused by the hyperaldosteronism, was almost completely abolished, and the increased potassium excretion returned to normal.

Renin, aldosterone, sodium and hypertension

Serum renin concentration and twenty-four hour urinary aldosterone excretion were determined in forty-nine normokalemic patients with uncomplicated essential hypertension. The serum renin values for the hypertensive patients on normal sodium intake were significantly lower than those in eleven normotensive subjects, but the urinary aldosterone values were not significantly elevated. Since the urinary sodium excretion in the hypertensive patients was significantly higher than in the normotensive subjects regardless of sodium intake, and since some of the hypertensive patients failed to achieve sodium balance on a low sodium intake regardless of normal clinical tests of kidney function, the hypertensive patients were subdivided into three groups according to the way in which they reacted to sodium restriction. Although there was a significant difference in the mean values for the excretion of sodium in two of the three groups, there was no significant difference in the mean values for serum renin concentration or urinary aldosterone excretion, suggesting that these two measurements were not directly related to sodium excretion. Our data failed to indicate a relationship between serum renin concentration or urinary aldosterone excretion and race in essential hypertension. Nor was a significant correlation found between serum renin and duration of hypertension, age or diastolic blood pressure. None of these patients was found to have normokalemic primary aldosteronism using the criteria of low fixed serum renin activity occurring with inappropriately increased aldosterone excretion.

Radioimmunological determination of plasma renin activity during the menstrual cycle and during acute progesterone administration.

ABSTRACT Antibodies to ileu5angiotensin I were produced in rabbits with the poly-l-lysine succinyl complex of angiotensin I. Iodine-125 was used for the labelling of angiotensin I. The tracer was purified on a G-15 Sephadex column. For the determination of plasma renin activity plasma samples containing EDTA and BAL were incubated for two hours at 37°C. while a parallel sample was kept at 4°C to serve as a plasma blank. The angiotensin I content in 50 μl of plasma diluted 1:20 was quantitated directly, without prior extraction. For the immunoassay the samples and standards were incubated with 125I-angiotensin I (about 2500 cpm) and antiserum at a final dilution of 1:50 000–1:60 000 for 16–18 hours at 4°C. Dextran-coated charcoal was used for the separation of free and antibody-bound angiotensin I. The antiserum did not bind angiotensin II. The lower limit of detection was 20 pg. An average recovery of added angiotensin I of 100.5 % ± 11 (sd) was obtained. In duplicate determinations a coefficient of variation of 6.9 % was found. The method was used to measure renin activity during the menstrual cycle. In the follicular phase a range of 0.8–1.5, mean 1.14 ng ang.I/ml/h, was found, whereas the values in the luteal phase were 2.1–4.0, mean 3.06 ng ang.I/ml/h, respectively. When 500 mg progesterone, divided into 5 doses over a period of 24 hours was given to menopausal women, an increase in renin activity was found. No increase in aldosterone excretion or in the K/Na ratio in the urine was observed during this period.

Hyperaldosteronism in hypertensive congenital adrenal hyperplasia.

The urinary steroid pattern was characterized in an 11-yr-old child with congenital adrenal hyperplasia, hypertension, and multiple adrenal rest tumors of the ovaries. Compensated 11β-hydroxylation deficiency was suggested by increased excretion of THS, TH-DOC and 11-desoxy-17-KS, and normal urinary THF and THE, THB, and 11-oxy-17-KS. A previously undescribed abnormality of unusual interest was the finding of increased aldosterone excretion, which fell to normal, as did the blood pressure, with effective adrenal suppression. This finding suggests that increased secretion of aldosterone as well as DOC may contxibute to the hypertension in this form of CAH.