Aldosterone Secretion In Man Research Articles

Dopaminergic regulation of 18-hydroxycorticosterone and aldosterone secretion in man.

This study was designed to investigate dopaminergic mechanisms involved in the control of corticosteroid secretion. Plasma renin activity (PRA), prolactin, cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone (18-OHB) and aldosterone responses to metoclopramide 10 mg iv in the presence of a vehicle or dopamine (3 microgram/kg/min) infusions, or domperidone 10 mg iv were evaluated in 10 normal males. Metoclopramide, and the peripheral dopamine antagonist, domperidone both resulted in rises in serum prolactin levels. Metoclopramide, but not domperidone, resulted in parallel rises in plasma 18-OHB and aldosterone levels. Dopamine infusion markedly inhibited prolactin, 18-OHB and aldosterone responses to the central and peripheral dopamine antagonist metoclopramide. Administration of the dopamine agonist, bromocriptine, 2.5 mg three times a day for 4 days suppressed (P less than 0.01) mean 24 h plasma 18-OHB levels from 22.1 +/- 2.1 to 15.8 +/- 1.5 ng/dl. These results suggest that dopaminergic mechanisms modulate the secretion of 18-OHB and aldosterone. The circadian rhythm of 18-OHB secretion is not dependent on dopaminergic mechanisms.

Plasma aldosterone response to acute stimulation in panhypopituitarism.

The influence of acute stimulation by ACTH, upright posture and angiotensin II on plasma aldosterone levels was assessed in human panhypopituitarism. While stimulation by ACTH in hypopituitary patients induced a plasma aldosterone increase similar to that observed in healthy controls, stimulation by upright posture or by infusion of angiotensin II resulted in a lower plasma aldosterone response than in controls in most of the patients. These results suggest that the presence of an anterior pituitary hormone, most likely ACTH, directly or indirectly exerts a permissive action on aldosterone secretion in man.

Dopaminergic modulation of aldosterone secretion in man is unaffected by glucocorticoids and angiotensin blockade.

This study examines the mechanism of dopaminergic modulation of aldosterone secretion in normal man. Nine normal male volunteers in metabolic balance at 100 meq sodium/ day and 60 meq potassium/day constant intake received metoclopramide (10 mg iv) with 5% dextrose (vehicle), with dopamine (3 eg/kg-min, with saralasin (10 eg/kg-min), or after 4 days of dexamethasone (2 mg orally every 6 h) or placebo. Metoclopramide in the presence of vehicle increased plasma aldosterone concentrations from 12.5 ± 1.2 to a maximum of 25.0 ± 2.5 ng/dl (P < 0.01) and serum PRL concentrations from 10.0 ± 1.1 to a maximum of 74.9 ± 8.6 ng/ml. The aldosterone and PRL responses displayed a parallel time course, with significant responses of both occurring 5 min after metoclopramide administration. A significant rise (P < 0.05) in plasma renin activity (PRA) from 2.7 ± 0.4 ng/ml h−1 to 4.5 ± 1.0 ng/ml h−1 was observed only at the 30-min sampling time. Dopamine infusion suppressed the aldosterone, PRL, and PRA responses to metocl...

Studies of Plasma Aldosterone in Anephric People: Evidence for the Fundamental Role of the Renin System in Maintaining Aldosterone Secretion*

When plasma aldosterone (PA) was measured in 32 predialysis samples from 18 anephric subjects more than 3 months postnephrectomy, all but two values were subnormal, 16 measurements were undetectable, i.e. below 0.35 ng/100 ml, and PA averaged only 1.7 ng/100 ml +/- 0.5 (SE) in the remaining 16. In contrast, PA averaged 29.7 +/- 5.6 ng/100 ml in 12 dialysis patients with kidneys. Plasma renin activity was undetectable in 15 assays of anephric subjects and averaged 0.5 +/- 0.1 ng/ml/h in the remaining 17. However, these latter measurements appeared to be an artifact caused by the presence of plasma prorenin. Serum potassium fell during dialysis and appeared responsible for the concurrent 75% fall in PA observed in six nephric patients (delta 14 ng/100 ml), and in three anephric patients (delta 3.3 ng/100 ml) with low but measurable PA values. Overt hyperkalemia was required for potassium to stimulate aldosterone into the normal range in anephric subjects. The angiotensin II analog, saralasin, also increased PA slightly in five studies. Renin and PA fell after nephrectomy and increased after transplantation. Decreases and increases in renin always preceded those of aldosterone. Usually it took several weeks for aldosterone to fall to undetectable levels and several days to return to normal levels after renal transplantation. These observations suggest that the baseline plasma level of angiotensin determines both the baseline level of aldosterone secretion and its capacity to respond either to more angiotensin or to other stimuli. In the absence of renin, the adrenal almost loses its capacity to generate aldosterone. The data support the view that the renin system plays a fundamental role in maintaining aldosterone secretion in man.

Effect of prolonged low-dose infusions of ile5-angiotensin ii on blood pressure, aldosterone and electrolyte excretion in sodium replete man.

Two healthy young males on a constant normal sodium diet (135 mM/day) were infused for 132 h with 3 ng/kg/min of angiotensin II. Plasma angiotensin II levels were therby raised to the range of moderate sodium depletion. Plasma aldosterone and the urinary excretion rate of aldosterone-18-glucuronide were markedly increased during the whole infusion period and returned to control levels after the infusion was stopped. A slight tendency of aldosterone secretion to decrease towards the end of infusion was probably due to sodium retention (appr. 200 mM and 350 mM respectively) and to a fall in plasma potassium by approximately 0.5 mM/1. Plasma aldosterone during infusion, maintained circadian variations similar to those of cortisol. Plasma cortisol patterns were unaffected by angiotensin II. Blood pressure increased gradually during angiotensin II infusion, reflecting changes in sodium balance. The results, differing from those of studies in dog and sheep, support the assumption that angiotensin II is an important regulator of aldosterone secretion in man rather than a merely permissive factor.

Sensitization of the adrenal cortex to angiotensin II in sodium-deplete man

The effect of sodium depletion on the dose-response relationships of angiotensin II to aldosterone and blood pressure was studied. Arterial plasma angiotensin II and aldosterone and arterial blood pressure were measured before and during the incremental infusion of angiotensin II into sodium-replete and sodium-deplete subjects. Sodium depletion caused a distinct steepening of the angiotensin Il-aldosterone dose-response curves in four of five subjects and a concurrent diminution in the pressor effect of angiotensin II. Administration of angiotensin II did not demonstrably alter the half-life of aldosterone. Sodium depletion did not change the plasma concentrations of sodium or potassium, but it was accompanied by a significant increase in plasma levels of 11-hydroxycorticosteroids and magnesium. The contrasting effects of sodium depletion on the aldosterone and the pressor dose-response curves favored sodium retention. These results are consistent with an important role for the renin-angiotensin system in the control of aldosterone secretion in man.

Studies on the control of aldosterone secretion in man

Plasma cortisol, plasma aldosterone and in some cases plasma renin activity (PRA) were measured in blood samples taken every 20 or 30 min overnight from recumbent sleeping subjects. In 9 control subjects peaks of aldosterone were matched by peaks of cortisol on all of 21 occasions and in 8 out of the 9 studies the plasma levels of the two steroids were significantly correlated. Of 11 peaks of PRA, only three were matched by aldosterone. Dexamethasone abolished cortisol secretion, but aldosterone secretion was unchanged. Long-term administration of propanolol or oxprenolol failed to suppress the episodic changes in PRA, and PRA levels were not suppressed, and neither was the episodic secretion of cortisol or aldosterone in two patients with high cervical spinal cord transection. PRA changes and aldosterone secretion continued in a hypophysectomised patient. In a patient studied after renal transplantation, changes occurred in PRA levels, but aldosterone secretion was low and fixed. It is concluded that cortisol secretion is mediated by ACTH, and that some other factor which is not the renin-angiotensin system, ACTH, sodium or potassium is responsible for mediating the episodic release of aldosterone and that it acts synchronously with, but independently of ACTH.

The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.

To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, which blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin II, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.

Inter-relationships between plasma angiotensin II, arterial pressure, aldosterone and exchangeable sodium in normotensive and hypertensive man

1. 1. Evidence bearing on the importance of the renin/angiotensin system in the regulation of aldosterone secretion in man is reviewed. 2. 2. Elevation of plasma angiotensin II concentration in simple dietary sodium deprivation has been confirmed. 3. 3. In primary renin deficiency, both angiotensin II and aldosterone are deficient. In these circumstances plasma aldosterone can remain unresponsive to very large rises in plasma potassium, but increase promptly on infusion of angiotensin II. 4. 4. Sodium depletion in normal man increases the adrenocortical sensitivity to angiotensin II, while diminishing the presser effect. 5. 5. The Na E/renin and Na E/angiotensin II interrelations are normal in primary hyper-aldosteronism both before and after treatment, and also in untreated essential hypertension with normal renin levels. 6. 6. These relationships are depressed in low-renin essential hypertension. 7. 7. In renal and malignant hypertension the relationships are enhanced. 8. 8. In renal and malignant hypertension the angiotensin II-pressor relationship is enhanced, and the angiotensin II-aldosterone relationship steepened as compared with normal subjects acutely infused with angiotensin. 9. 9. A hypothetical mechanism for the suppression of renin in essential hypertension is outlined.

Sensitization of the Adrenal Cortex to Angiotensin II in Sodium-Deplete Man

The effect of sodium depletion on the dose-response relationships of angiotensin II to aldosterone and blood pressure was studied. Arterial plasma angiotensin II and aldosterone and arterial blood pressure were measured before and during the incremental infusion of angiotensin II into sodium-replete and sodium-deplete subjects. Sodium depletion caused a distinct steepening of the angiotensin Il-aldosterone dose-response curves in four of five subjects and a concurrent diminution in the pressor effect of angiotensin II. Administration of angiotensin II did not demonstrably alter the half-life of aldosterone. Sodium depletion did not change the plasma concentrations of sodium or potassium, but it was accompanied by a significant increase in plasma levels of 11-hydroxycorticosteroids and magnesium. The contrasting effects of sodium depletion on the aldosterone and the pressor dose-response curves favored sodium retention. These results are consistent with an important role for the renin-angiotensin system in the control of aldosterone secretion in man.

Aldosterone: Physiological and pathophysiological variations in man

By virtue of its profound effects on sodium and potassium metabolism, changes in which have general repercussions in all tissues, aldosterone performs an important role in the normal physiology and pathophysiology of man. There is an abundance of circumstantial evidence, much of which is presented in the present paper, that the renin-angiotensin system exerts a major influence on aldosterone secretion in man. Moreover, the study of the patient described in the last section, in whom very low plasma aldosterone levels were associated with low levels of renin and angiotensin in the absence of any other detectable abnormality in adrenocortical control, and in whom plasma aldosterone levels could be corrected solely by angiotensin 11 infusion, provides more direct evidence of this relationship. The assumption of the importance of the renin-angiotensin system in this respect, and also the relatively recent possibility of measuring accurately the several components of this system, has allowed an understanding of the aetiology of many types of hypertensive and circulatory disease. It must, however, be emphasised that much has still to be learned of the nature of adrenal aberrations leading to abnormal control of electrolyte metabolism and arterial blood pressure. For example, detailed studies of non-aldosterone hypermineralocorticoidism are extremely few, partly due to the lack of suitable analytical techniques for many of the steroids which may be implicated, and possibly also to the apparent rarity of patients suffering from these conditions. Again, the aetiology of hyperaldosteronism associated with low plasma renin in which only adrenocortical hyperplasia or micronodular hyperplasia is found at surgery also raises the possibility of the existence of some as yet unknown adrenocortical trophic substance. Perhaps a final understanding of the control of electrolyte metabolism, blood pressure and the status of aldosterone will be obtained only when simultaneous study of metabolic, endocrine and cardiovascular changes becomes possible. The use of computer-assisted systems analysis such as has been developed by Guyton and his colleagues ( Guyton and Coleman, 1969 ), may be a first step in this direction.

The Relationship between Angiotensin and Aldosterone

Publisher Summary Angiotensin plays an important part in the physiological control of aldosterone secretion. Although the precise role of the renin-angiotensin system in the physiological control of aldosterone secretion is yet to be defined, the investigation of this relationship has nonetheless yielded extremely useful information clinically. The angiotensin II can stimulate aldosterone secretion in man, and where circulating angiotensin II levels are high there is commonly a state of hyperaldosteronism. By contrast, when there is a primary increase in aldosterone secretion, the plasma renin activity and circulating plasma angiotensin II levels are often secondarily suppressed. The carcinoma of the adrenal cortex causes a clinical syndrome that is indistinguishable from the more common adenoma although steroid analysis usually distinguishes this group by demonstrating an increased cortisol production in those cases where aldosterone secretion is increased. The generally accepted proposition that the secondary aldosteronism associated with a variety of physiological and pathological states is because of increased activity of the renin–angiotensin system lacks critical proof.

Renin and aldosterone secretion in man as influenced by changes in electrolyte balance and blood volume.

In six normal volunteers maintained on a constant dietary intake, serial studies were made of plasma renin activity, blood volume, aldosterone secretion and sodium balance, first following dietary and diuretic-induced depletion of sodium and blood volume, then following a period of sodium repletion during a maintained reduction in blood volume, and finally after blood volume repletion. In the first phase, during which depletion of blood volume paralleled sodium depletion, renin and aldosterone secretion were both increased. Under the circumstances of a subsequent study period, however, it was possible to separate the effects of sodium depletion from those of reduction in total blood volume. In this period, the administration of sodium chloride was associated with an increased urinary sodium excretion and a marked suppression of plasma renin and aldosterone secretion at a time when total blood volumes were maintained below control values by repeated plasmapheresis and phlebotomy. This sodium-dependent suppression of renin and aldosterone secretion may have been mediated by an expansion in extravascular fluid volume(s). However, the observed effects are perhaps better explained in terms of an induced change in intrarenal tubular sodium transport. The parallelism observed between the changes in renin and aldosterone secretion suggests that under the conditions of these studies renin plays a major role in regulating aldosterone secretion.

The control of aldosterone secretion and its relationship to the diagnosis of hyperaldosteronism.

Current concepts of the control of aldosterone secretion in man have been reviewed with particular reference to the role of the kidney. On the basis of these concepts, it is concluded that hyperaldosteronism is most conveniently diagnosed by repeated estimation of plasma potassium, which is usually persistently or intermittently reduced in this disease. Occasional cases fail to show hypokalaemia. Distinction between primary and secondary hyperaldosteronism is made by means of measurement of plasma renin concentration. Subnormal values are usually obtained in the first instance and supranormal values in the second.

The regulation of aldosterone secretion in man: the role of fluid volume.

The regulation of aldosterone secretion in man: the role of fluid volume.

Observations on the regulatory mechanisms of aldosterone secretion in man.

The regulatory mechanisms governing aldosterone secretion in man are as yet obscure. Axelrad and Leutscher1have shown that a fivefold increase in urinary aldosterone occurs in man when the dietary sodium is restricted. Laragh and Stoerk2have suggested that serum potassium is a powerful direct or indirect stimulus to aldosterone secretion and that increases in urinary aldosterone on dietary sodium restriction are mediated by an alteration in serum potassium or Na/K ratio. Although corticotropin does not appear to affect either the excretion * or the blood levels of aldosterone in normal persons,4Gordon and co-workers5have found an increase in the output of this sodiumretaining hormone in a patient with rheumatoid arthritis following the intravenous administration of corticotropin. Leutscher and Axelrad6have observed essentially normal levels of urinary aldosterone in patients with panhypopituitarism. It has been sug- gested by Peters7that the mineralocorticoid output of