Urinary Aldosterone Excretion Research Articles

Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies

Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p < 0.01 and p < 0.05, respectively) in the patients with Basedow's disease than in the normal subjects, whereas basal PA level was similar in the two groups. The ACTH injection induced similar increases in plasma cortisol, plasma 18-hydroxycorticosterone (18-OHB) and PA in the two groups. The graded AII infusions also produced increases in plasma 18-OHB and PA in the two groups. Responses of these two corticosteroids to AII were, however, significantly lower (p < 0.05) in the patients with Basedow's disease than in the normal subjects. In the experimental animal study, basal PRA levels and the adrenal glomerulosa cell count/adrenal were significantly higher (p < 0.05) in the H-rats than in the control rats, whereas basal PA levels were similar in the two groups. Aldosterone production in response to AII, ACTH, and potassium increased in a dose-dependent manner in the two groups. Responses of aldosterone production to AII were, however, significantly lower (p < 0.05) in the H-rats than in the control rats. These results suggest that the impaired responsiveness of adrenal zona glomerulosa cells to AII, as well as an increased metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

The role of the adrenal gland in hypertensive transgenic rat TGR(mREN2)27.

The TGR(mREN2)27 is a new monogenetic rat model in hypertension research. As the mouse Ren-2d renin gene is integrated into their genome, they develop fulminant hypertension between 5 and 15 weeks of age, with blood pressure maxima of 300 mm Hg. Their plasma renin-angiotensin system (RAS) is suppressed, but the transgene is highly expressed in the adrenal gland, so we investigated its possible role in steroid metabolism and the pathogenesis of hypertension. During the phase of hypertension development (between 6-18 weeks), the urinary excretion of deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone, and aldosterone is 1.5- to 2.5-fold elevated compared with that in Sprague-Dawley (SD) rats (P less than 0.0005) despite the suppressed plasma RAS. Moreover, the adrenal gland in TGR(mREN2)27 shows an increased maximal response to ACTH stimulation in regard to urinary excretion of DOC (after ACTH, 244 +/- 42 ng/24 h in TGR; 62 +/- 10 ng/24 h in SD; P less than 0.0005) and B (after ACTH, 5144 +/- 346 ng/24 h in TGR; 2607 +/- 324 ng/24 h in SD; P less than 0.0005). Additionally, plasma prorenin in TGR was stimulated more than 10-fold, indicating transgene regulation by ACTH. Since spironolactone treatment did not lower the blood pressure in TGR, hypertension solely due to hypermineralocorticoism is unlikely. Our results indicate that the adrenal steroid metabolism is markedly stimulated in young TGR, and the absolute increase in urinary DOC and B after ACTH injections is enhanced, possibly due to a stimulated local intraadrenal RAS.

Cellular origin of aldosteronomas.

In the 1950s, after years of suspicion and work by many investigators regarding a potent mineralocorticoid hormone from the adrenal cortex, aldosterone was at last isolated and chemically identified [40, 41]. Soon after, Jerome Conn was the first to report [11] the clinical correlate of excessive secretion of aldosterone from a benign adrenocortical tumor manifested by hypertension and hypokalemia with the increased urinary excretion of aldosterone. This tumor is often called as aldosteronoma, and the disorder produced by it has been called primary aldosteronism by Conn. In the vast majority of patients harboring such tumors, the hypertension is cured by the resection of the tumor [12, 51], although some suggest that the hypertension may recur in a proportion of apparently cured patients [3, 36]. Thus, primary aldosteronism represents one of a few potentially curable forms of hypertension. Since aldosterone is elaborated normally by the zona glomerulosa cells of the adrenal, it has been assumed that all aldosteronomas originate from the cells of the glomerulosa zone. A clonal origin of aldosteronomas has also been suggested [28]. Some earlier and recent developments, however, indicate that functionally there may be more than one type of aldosteronomas and that their cellular origins might be different.

Genetic influences on the urinary excretion of aldosterone in children.

Several studies have shown an inverse relation between blood pressure and plasma aldosterone levels. Since blood pressure is in part genetically regulated, we looked for evidence that genetic factors might also affect aldosterone production. The nocturnal urinary excretion rate was used to estimate aldosterone production, and electrolyte excretion rates were used to estimate sodium and potassium intakes. Studies were carried out in monozygotic (MZ) (n = 37 pairs) and dizygotic (DZ) (n = 26 pairs) twins, aged 6-17 years. Both groups of twins were white. The intraclass correlation coefficient for aldosterone excretion was 0.686 (p = 0.0001) for MZ twins, and 0.290 (p = 0.079) for DZ twins, indicating high heritability for the aldosterone excretion rate. In a second study, we looked for a racial effect on the genetic regulation of aldosterone excretion. Siblings from both black and white families (72 black siblings and 157 white siblings) were selected from an ongoing longitudinal study. Mean values for nocturnal aldosterone excretion, rates measured every 6 months over 1.5-3.5 years, were used in the analysis. The intraclass correlation coefficient for aldosterone excretion, adjusted for sodium and potassium excretion, was 0.510 (p = 0.001) for black siblings and 0.087 (p = 0.228) for white siblings, indicating a strong familial aggregation for aldosterone excretion in black children. In conclusion, studies in twins showed that regulation of urinary aldosterone excretion in children is determined partially by genetic factors. A familial component affecting the aldosterone excretion rate appears to be much stronger in blacks than in whites.

Hemodynamic Responses to Verapamil Monotherapy in Patients With Renal Disease

We have explored the effect of verapamil on renal hemodynamics and the renin-aldosterone system in ten patients with chronic renal disease and hypertension before and after 3 months of therapy. The mean +/- SEM glomerular filtration rates were 55 +/- 7 mL/min pre- and 55 +/- 8 mL/min posttherapy; the renal plasma flow was 231 +/- 29 mL/min pre and 244 +/- 35 mL/min posttherapy. The filtration fraction (0.24 pre; 0.23 post) and the renal vascular resistance (492 +/- 144 pre; 422 +/- 101 post) also remained stable with verapamil therapy. Blood pressure was lower after treatment (P less than .02) in 7 of 10 patients. Urinary albumin excretion was reduced only when blood pressure was lowered. Verapamil had a modest effect on the renin-aldosterone axis. While the mean increase in plasma renin activity from a pretreatment value of 1.8 +/- 0.42 ng/mL/h to 2.1 +/- 0.56 ng/mL/h failed to reach statistical significance, the increases in urinary aldosterone excretion from 8.2 +/- 2.2 mg/24 h to 11.1 +/- 2.3 mg/24 h did (P less than .001). Our results demonstrate that verapamil lowered blood pressure without renal hemodynamic compromise in hypertensive patients with chronic renal disease. The antihypertensive response was associated with a rise in urinary aldosterone excretion, with unchanged serum electrolytes. We conclude that verapamil is effective, safe, and well-tolerated in patients with renal impairment and hypertension, and may be suitable for clinical trials evaluating long-term progression of renal disease.

Hormonal effects of the diuretic xipamide in healthy men

The effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system have been studied in 12 healthy men, using a double-blind cross-over design. After a run-in period on placebo of 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained reduced. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in hematocrit and hemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the hematocrit and hemoglobin. The changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.

Hyaline Membrane Disease and Early Neonatal Aldosterone Metabolism in Infants of Less than 33 Weeks Gestation

We studied urine excretion of free and conjugated aldosterone by 12 control infants and 14 infants with hyaline membrane disease (HMD) on the first and seventh days after birth. Both groups had a mean gestational age of 29 weeks. Total urine aldosterone excretion (UAE) and percent excreted as conjugate were similar for both groups on both study days, and did not relate to the severity of respiratory failure in infants with HMD. Sodium intake was higher for infants with HMD on both study days (p less than 0.02), but their urine sodium excretion was only significantly (p less than 0.01) higher on day 7. For total UAE values greater than 3 nmol/kg/d, there was no significant difference between estimated sodium-potassium exchange by control (22 +/- 5%, n = 8) and HMD (31 +/- 5%, n = 10) groups. These data suggest that neither the magnitude of excretion of aldosterone in the urine, the ability to conjugate aldosterone nor the degree of relative distal tubular unresponsiveness to aldosterone are related to the severity of pulmonary immaturity in preterm infants.

Ammonium chloride metabolic acidosis and the activity of renin-angiotensin-aldosterone system in children

The present study was undertaken to assess the effects of acute metabolic acidosis on the activity of the renin-angiotensin-aldosterone system in 12 children with a mean age of 8.9 years who underwent NH4Cl loading test. Ammonium chloride was given in a dose of 0.15 g/kg per day for 3 consecutive days to evaluate renal acidification. Prior to and following NH4Cl administration blood acid-base parameters, plasma and urine electrolytes, creatinine and aldosterone concentrations as well as plasma renin activity (PRA), urine flow rate and net H+ excretion were measured. Ammonium chloride administration significantly depressed blood pH (P less than 0.05), bicarbonate (P less than 0.01) and base excess (P less than 0.01) and resulted in a slight, but significant elevation of plasma potassium concentration (P less than 0.05). Furthermore, NH4Cl ingestion induced a marked increase in urine flow rate (P less than 0.01) and urinary sodium, potassium and chloride excretion (P less than 0.01). In response to NH4Cl metabolic acidosis, PRA doubled (4.72 +/- 1.18 vs 8.13 +/- 1.02 ng/ml per hour, P less than or equal to 0.05) and there was a nearly four-fold increase in plasma aldosterone level (0.49 +/- 0.12 vs 1.52 +/- 0.24 ng/ml, P less than 0.01) and in urinary aldosterone excretion (19.2 +/- 4.3 vs 71.8 +/- 13.8 micrograms/day, P less than 0.01). The elevated aldosterone production observed in this study is assumed to be mediated by the combined effect of sodium and water diuresis-related increased PRA, hyperkalaemia and the direct stimulation of adrenal steroidogenesis by metabolic acidosis.

Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis

It has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin-aldosterone and sympathetic nervous systems. To test this hypothesis, systolic blood pressure, sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals. No significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study. The eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion. At the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected. These changes were more marked the ninth week of the study. In cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion. Postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them. These results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is chronologically related to a significant decrease in arterial pressure, thus supporting the "peripheral arterial vasodilation hypothesis" of ascites.

Hypoaldosteronism — Disease or Normal Response?

IN 1957 Hudson et al.1 described a patient with isolated hypoaldosteronism who had hyperkalemia with low urinary aldosterone excretion, normal glucocorticoid secretion, and relatively normal renal ...

A close relationship between the renal potassium regulation and the maximum binding of ouabain to erythrocytes

Maximum binding of ouabain to erythrocytes (Bmax), serum K, urinary aldosterone excretion (U-Aldo) and fractional excretion of filtered K (FEK) were examined in 69 healthy children aged 12 to 15 years to assess the relationship between the sodium pump receptor in erythrocytes and the renal handling of potassium (K). Bmax showed a significant negative correlation with FEK. Subsequently, FEK showed a negative correlation with serum K which was within normal range in every child, and a positive correlation with U-Aldo. However, Bmax showed no correlation with serum K or U-Aldo. These findings suggest that aldosterone may influence Bmax via the changes in FEK and serum K within physiological ranges. In other words, there can exist a close relation between Bmax and the renin-angiotensin-aldosterone system through K metabolism.

Long-term Effects of Delapril on Renal function and Urinary Excretion of Kallikrein, Prostaglandin E2, and Thromboxane B2 in Hypertensive Patients

The effects of delapril, an angiotensin converting enzyme (ACE) inhibitor, on renal function and the renin-angiotensin and kallikrein-prostaglandin systems were investigated in 10 hypertensive patients who were treated for between 4 months and 1 year. There was a significant (P less than .05) increase in renal blood flow (RBF) without affecting glomerular filtration rate. Filtration fraction increased, while renal vascular resistance decreased. There were also significant (P less than .05) increases in urinary kallikrein and prostaglandin excretion, while thromboxane excretion decreased. There was no change in urinary aldosterone excretion. These results suggest that renal hemodynamic changes seen during long-term therapy with delapril are caused, in part, by activation of the kallikrein-prostaglandin system, as well as suppression of the renin-angiotensin system.

Renal Function Derangements Induced by Portacaval Anastomosis in Normal Rats

The purpose of this study was to determine the renal function derangements that portacaval shunting caused in previously normal rats. Eight rats suffered a surgical portacaval shunt (PCS) and another 8 a sham operation (SHAM). Renal function was investigated by determining urinary volume, sodium, potassium, creatinine and aldosterone excretion, in basal conditions and after sodium overload. Plasma renin concentration and urinary excretion of PGE2, 6-keto-PGF1 alpha and TXB2 were also determined in basal conditions. PCS rats showed increased urinary volume, creatinine excretion and endogenous creatinine clearance, either in basal conditions or after sodium load. After the latter, PCS animals also showed sodium retention and hyperaldosteronuria. PCS caused in basal conditions a striking diminution in urinary excretion of all prostaglandins and no changes in plasma renin. In conclusion, PCS in the normal rat caused a renal dysfunction consisting of polyuria, possibly related to ADH disfunction and an inability to manage a sodium load.

Nisoldipine—effects on the renin‐angiotensin‐aldosterone system and catecholamines. Studies in normotensive and hypertensive subjects

We have studied the effects of nisoldipine, a new calcium channel antagonist, on the renin-angiotensin-aldosterone system and on plasma catecholamines in 10 healthy volunteers and in 29 patients with primary essential hypertension. Of these 29 patients, thirteen had normal renin hypertension (NRH), and sixteen had low renin hypertension (LRH). Eight healthy volunteers received placebo. Short-term (24 h) effects were measured in all subjects and long-term (up to 6 months) effects of 10-40 mg nisoldipine daily were monitored in the 29 hypertensive patients. Plasma renin activity (PRA) increased slightly, although this rise was not statistically significant, 1 h after the first dose of nisoldipine in both normotensive subjects and hypertensive patients. After 2 h PRA had returned to the pre-treatment level. No change in PRA was observed after administration of placebo. Plasma angiotensin II (AII) levels showed considerable variation after nisoldipine administration. Plasma aldosterone levels decreased despite the increase in PRA and AII concentrations. However, no concomitant reduction in urinary aldosterone excretion was observed. Plasma noradrenaline levels increased slightly 2-4 h after administration of nisoldipine, and decreased again thereafter, but no changes in plasma adrenaline levels were seen. Nisoldipine had no long-term effects on the renin-angiotensin-aldosterone system or on serum catecholamine levels.

Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: Deviations related to the development of superimposed preeclampsia

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis. (AM J OssTET GYNECOL 1990;163:1612-21.)

Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects.

The effects of an orally active inhibitor (UK 79300) of the neutral metalloendopeptidase EC 3.4.24.11 were investigated in six healthy male volunteers maintained on a constant diet (150 mmol sodium/day and 80 mmol potassium/day). Subjects were studied in a random order, single-blind study on two occasions, each 48 hours in length, when they were given UK 79300 (25 or 50 mg p.o.) or placebo at 12-hour intervals (each agent for 24 hours). The endopeptidase inhibitor enhanced plasma concentrations of atrial natriuretic factor in association with suppression of both plasma renin activity and aldosterone concentrations. Twenty-four-hour urinary excretion of sodium was doubled by UK 79300, and the urinary excretion rates of phosphorus, atrial natriuretic factor immunoreactivity, and cyclic guanosine monophosphate were also significantly enhanced, whereas urinary aldosterone excretion was halved. The profile of biological effects closely paralleled those previously reported with low dose infusions of atrial natriuretic factor in humans and animals. Therapeutic trials of such inhibitors are now indicated for hypertension or heart failure together with further studies to clarify the underlying mechanisms of action.

Primary aldosteronism: Study of twenty-six operated cases

A follow-up study of 26 patients operated on for suspicion of primary aldosteronism was made. The preoperative investigative procedures, including serum potassium concentration, urinary aldosterone excretion, and plasma renin activity, could not differentiate between patients with or tical adenomas and those with cortical hyperplasia or normal glands. Preoperative roentgenologic examinations visualized only one third of the adenomas. Altogether 44 of the 52 suprarenal glands had to be explored to reveal the 21 adenomas. Patients with cortical adenoma often became normotensive, in contrast to those with cortical hyperplasia or normal adrenal glands histophathologically. The suprarenal glands were explored from behind according to Nesbit. The complications were few and minor.

Systemic and renal effects of a new angiotensin converting enzyme inhibitor, benazepril, in essential hypertension

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.

Captopril Treatment in Bartter's Syndrome

A 13-year-old girl presented with lassitude, polyuria and hypokalemia. Plasma renin concentration and urinary prostaglandin excretion were elevated, whereas plasma aldosterone concentration, urinary aldosterone excretion and blood pressure were normal. A diagnosis of Bartter's syndrome was made. The result of treatment with oral potassium was unsatisfactory. Treatment with acetylsalicylic acid had some effect, but an allergic reaction rendered withdrawal necessary. Treatment with the angiotensin converting enzyme inhibitor captopril and oral potassium led to clinical and biochemical improvement.

Angiotensin-Converting Enzyme (ACE) Inhibition Therapeutic Option for Diabetic Hypertensive Patients

When choosing antihypertensive agents for the treatment of diabetic patients with hypertension, it is necessary to consider the individual characteristics of these patients. In this respect, angiotensin-converting enzyme (ACE) inhibitors constitute an attractive option for diabetic patients. The effects of enalapril alone for 16 weeks in 23 non-insulin-dependent diabetic (NIDD) patients and in 10 non-diabetic patients with mild to moderate essential hypertension (EH) [diastolic blood pressure greater than 95 mm Hg and less than 115 mm Hg] were evaluated. Similar reductions in both systolic and diastolic blood pressure were observed in 17 NIDD patients (from 155 +/- 18/100 +/-11 mm Hg to 128 +/- 12/82 +/- 8 mm Hg, respectively) and in 6 EH patients (from 155 +/- 21/100 +/- 6 mm Hg to 125 +/- 20/84 +/- 8 mm Hg, respectively) who achieved and maintained blood pressure control (diastolic blood pressure less than 90 mm Hg) for 16 weeks. In 4 NIDD and 4 EH patients blood pressure was not controlled. Two NIDD patients discontinued the medication, one because of symptomatic postural hypotension and the other, who had a plasma creatinine level of 1.8 mg/dl, because of hyperkalaemia (K = 6.1 mEq/L). In the responders, enalapril did not alter glucose tolerance, plasma or urinary excretion of creatinine, potassium, sodium and aldosterone. Plasma renin activity increased in the NIDD group only. In 11 patients (6 NIDD and 5 EH), the elevated protein or albumin excretions decreased. It is concluded that enalapril is a good therapeutic option for NIDD patients with hypertension.