Increase In Plasma Aldosterone Concentration Research Articles

Erythrocyte cation fluxes during the menstrual cycle in normal female subjects.

1. Studies of erythrocyte cation transport mechanisms in vitro were performed on eight normotensive, premenopausal female subjects at the mid-points of the follicular and luteal phases of their menstrual cycles. Concurrent plasma concentrations of 17 beta-oestradiol, progesterone, aldosterone and renin activity were measured. 2. Ouabain-resistant, frusemide-resistant rubidium influx (an index of passive potassium diffusion) was significantly lower in the luteal than the follicular phase. 3. In further studies in four of the eight subjects, the mean rate constant of the rubidium influx measurement was also lower in the luteal than in the follicular phase. 4. There were no changes in Na+-K+ co-transport, sodium pump activity or intracellular cation concentrations throughout the cycle. 5. There was a tenfold fall in the mean plasma 17 beta-oestradiol/progesterone ratio, as well as increases in plasma aldosterone concentration and renin activity between the mid-follicular and mid-luteal phases. 6. We conclude that changes in plasma oestrogen/progesterone ratio during the menstrual cycle may be associated with alterations in passive potassium diffusion.

Persistent tubular resistance to aldosterone in infants with congenital hydronephrosis corrected neonatally

Renal function of 18 infants who had undergone surgery in the neonatal period because of severe congenital hydronephrosis was followed up for 5 to 36 months (mean +/- SD 21 +/- 10 months). In all cases the diagnosis was made prenatally by sonography and confirmed at birth by intravenous urography. Creatinine clearance developed normally in all the children. Eight had a reduction in maximal urinary concentrating ability after intranasal DDAVP; this defect was transient and resolved after 4 to 5 months in all but one child, in whom it persisted. However, other tubular abnormalities were present. Throughout the observation period, patient serum potassium concentrations were significantly higher than normal, paralleled by a significant increase in plasma aldosterone concentration but with normal excretion fraction of sodium and potassium. There were no disturbances of acid-base balance. These findings may be accounted for by a persistent partial reduced sensitivity of the distal tubule to the action of aldosterone despite normal renal function. This alteration is usually mild, but may constitute a persistent metabolic risk despite successful surgical intervention.

Plasma renin activity and aldosterone concentration in sodium-depleted cattle following ACTH or metoclopramide injection.

Adrenocorticotropic hormone (ACTH) treatment (7 micrograms X kg-1 body weight) induced an increase in plasma aldosterone concentration in both Na-deficient heifers (following saliva loss after right parotid duct cannulation) and Na-replete heifers, but had no significant effect on plasma renin activity in either of these groups. The dopamine antagonist, metoclopramide, injected i.v. (1 mg X kg-1 body weight) did not modify plasma renin activity, aldosterone or cortisol concentrations in either group. These results indicate that dopamine did not play a major role in the regulation of aldosterone secretion in Na-replete or Na-depleted heifers.

Elevation of plasma aldosterone levels of tadpoles at metamorphic climax

Plasma aldosterone concentrations in Rana catesbeiana tadpoles during metamorphosis were determined by radioimmunoassay. Aldosterone levels were relatively low (0.7 – 1.4 ng/ml) during pre- and prometamorphosis. At the onset of climax, aldosterone concentration increased markedly and reached a peak (10.9 ng/ml) at stage XXII. Subsequently, aldosterone levels declined and at the end of metamorphosis (stage XXV), the average concentration was 3.9 ng/ml plasma. Administration of ACTH elevated plasma aldosterone levels in hypophysectomized tadpoles. When hypophysectomized animals were kept in thyroxine (T 4), plasma aldosterone concentrations also increased. Combined ACTH and T 4 treatment caused a marked increase in plasma aldosterone concentration. The possible involvement of thyroid hormone in the elevation of plasma aldosterone during metamorphosis is discussed.

Potassium regulation and progesterone-aldosterone interrelationships in human pregnancy: A prospective study

Little is known about the intrinsic renal and hormonal regulation of potassium excretion in pregnancy despite major alterations in many of the potassium regulatory factors. Forty primigravid women on an unrestricted diet were studied during the second and third trimesters and exhibited constant absolute and fractional potassium excretion despite a significant increase in plasma aldosterone concentration between these stages. The plasma progesterone level rose significantly between studies but closer analysis showed no correlation between individual changes in plasma aldosterone concentration and progesterone between trimesters. In the 14 subjects studied post partum, baseline absolute potassium excretion was not significantly altered but filtered potassium fell and fractional potassium excretion tended to rise. After dietary sodium manipulation at these stages, absolute potassium excretion, fractional potassium excretion, and progesterone were unaltered despite significant changes in plasma aldosterone concentration and sodium excretion. These results suggest that potassium excretion is held constant throughout pregnancy and that renal tubular potassium reabsorption adjusts appropriately to the increased filtered potassium load. Progesterone does not appear to be involved in the acute regulation of potassium or sodium excretion but may have effects on sodium and potassium excretion that are constant, proportional to its placental production, and unresponsive to endogenous changes in mineralocorticoid production.

Increased arterial potassium transport in reduced renal mass hypertension of the rat.

Aortic potassium turnover was studied during the development of hypertension induced by salt load in male rats after 70-75% of total renal mass was removed. Systolic blood pressure in the saline-drinking experimental reduced renal mass (RRM) rats steadily increased until the fourth week after surgery and thereafter stayed at the same level. Control RRM rats given tap water for drinking, and unilaterally nephrectomized saline-drinking control rats maintained normal blood pressure. Compared to controls, experimental RRM rats exhibited increased plasma aldosterone concentration while plasma renin activity was low in all groups with no significant difference. Aortic hypertrophy, greater 42K turnover, and elevated 42K exchange were observed with experimental RRM hypertension. Sensitivity to the effect of norepinephrine (NE) on aortic 42K turnover was increased four- to ninefold in the experimental RRM group as compared to controls. These results indicate that reduced renal mass hypertension is associated with increased potassium permeability and NE supersensitivity in vascular smooth muscle.

Role for aldosterone in blood pressure regulation of obese adolescents

To determine the role of aldosterone in the regulation of blood pressure (BP) in obese adolescents, supine and 2-hour upright plasma renin activity (PRA), and aldosterone and cortisol were measured in 10 nonobese and 30 obese adolescents before and after a 20-week weight loss program. The obese adolescents had significantly higher supine and 2-hour upright plasma aldosterone concentrations (17 ± 8 vs 6 ± 2 ng/dl [p < 0.01 supine obese vs nonobese] and 30 ± 11 vs 14 ± 8 ng/dl [p < 0.01 2-hour upright]). Although PRA was not significantly different between the 2 groups of children, a given increment in PRA produced a greater increment in aldosterone in the obese adolescents. In addition, obese subjects had a significantly increased mean BP (93 ± 12 vs 74 ± 8, p < 0.005) and a weak correlation between BP and plasma aldosterone concentration. Compared with an obese control group, weight loss resulted in a significant decrease in plasma aldosterone (p < 0.01) without an associated decrease in PRA. After weight loss there was also a significant decrease in the slope of the posture-induced relation between PRA and aldosterone. In addition to weight loss being associated with a significant decrease in BP (p < 0.01), there was a significant correlation between the change in plasma aldosterone and the change in mean BP (r = 0.538; p < 0.002 change in upright aldosterone vs change in mean BP). Obese adolescents have an increased plasma aldosterone concentration that may be important in the regulation of their BP.

Aldosterone regulates salivary sodium secretion in cattle.

Intravenous infusion of aldosterone (10 microgram/kg body wt per h for 5 h) in four 2-month-old calves decreased salivary and urinary sodium (Na+) concentration and increased salivary potassium (K+) concentration without modifying salivary flow or urinary K+ concentration. Intravenous angiotensin II infusion (0.3 microgram/kg body wt per min for 1 h) in four Na+-replete 16-month-old bulls decreased salivary Na+ concentration and increased that of K+. It also increased plasma cortisol and plasma aldosterone concentrations, and decreased plasma renin activity (PRA). In four 16-month-old bulls Na+ deficiency (induced by chronic cannulation of the right parotid duct and loss of saliva for 5 days) had similar effects to those observed following aldosterone infusion in calves: a decrease in salivary Na+/K+ ratio. This decrease was associated with an increase in PRA and an increase in plasma aldosterone concentration. In these animals a close positive relationship was observed between PRA and plasma aldosterone concentration (r = 0.91; n = 20; P less than 0.01). Thus in cattle, during Na+ deficiency, the effect of aldosterone on parotid glands participates in the regulation of Na+ metabolism.

Effect of bromocriptine treatment on the aldosterone response to angiotensin II and adrenocorticotropin in idiopathic hyperaldosteronism.

Bromocriptine can prevent an increase in plasma aldosterone during the infusion of angiotensin II in normal subjects and during upright posture in some patients with idiopathic hyperaldosteronism. To determine if bromocriptine prevents the increase in plasma aldosterone concentration during angiotensin II infusion in idiopathic hyperaldosteronism, we infused angiotensin II in five patients with idiopathic hyperaldosteronism, before and after treatment with bromocriptine (2.5 mg, three times daily for 5 days), and measured the resulting plasma aldosterone and angiotensin II concentrations. We also determined the adrenal response to ACTH infusion before and after bromocriptine treatment in four of these patients. Bromocriptine treatment did not significantly change the plasma concentrations of aldosterone before or during the infusions of angiotensin II and ACTH. It did significantly decrease mean blood pressure and increase the plasma corticosteroid concentrations in the preinfusion periods, but it did not alter the response of blood pressure to angiotensin II or of plasma corticosteroid concentrations to the ACTH infusions.

Stress and ACTH stimulate aldosterone secretion in the fowl ( Gallus domesticus)

1. 1. Temporal and dose-related effects of adrenocorticotrophin (ACTH) on the concentrations of plasma aldosterone have been determined in immature (5-week-old) and adult (20-week-old) domestic fowl. The influences of handling stress on aldosterone secretion has also been assessed. 2. 2. ACTH maximally increased plasma aldosterone concentrations 30 min after i.v. administration. In both immature and adult birds the aldosterone response was dose-related. In both cases the minimum response was induced by 1.0 i.u. ACTH/kg; higher doses (up to 20.0 i.u./kg) progressively increasing the aldosterone concentration. The aldosterone responses of adult birds to 5.0, 10.0 and 20.0 i.u. ACTH/kg were greater than those in immature birds. 3. 3. Plasma aldosterone responses to ACTH were less than plasma corticosterone responses. 4. 4. The stress of handling and bleeding increased the aldosterone and corticosterone concentrations in immature birds. Both hormones were increased within 3 min of initial handling. The aldosterone and corticosterone levels in birds that were serially bled were higher than those that were held and bled only once. 5. 5. These results demonstrate that the activation of the hypothalamo-pituitary adrenal axis stimulates in vivo aldosterone release in birds.

6-methoxy-tetrahydro-β-carboline (pinoline): effects on plasma renin activity and aldosterone, TSH, LH and β-endorphin levels in rats

Plasma renin activity and the plasma concentrations of aldosterone, TSH, LH and beta-endorphin were radioimmunologically determined in rats after ip administration of 15 mg/kg of 6-methoxy-tetrahydro-beta-carboline (6-MeO-THBC, pinoline), a compound found to occur normally in mammalian and avian pineal gland. A 2.6-fold increase of plasma aldosterone concentration was found and it was preceded by increase of plasma renin activity. An increase was also found in beta-endorphin/beta-lipotrophin concentration while TSH and LH concentrations did not change significantly. The present results do not prove nor exclude the concept that 6-MeO-THBC is the 'adrenoglomerulotropin'. The effects of 6-MeO-THBC on plasma beta-endorphin/beta-lipotrophin levels may be mediated by the dopaminergic or 5-HT-neurones.

Urinary Potassium Excretion in the Critically III Neonate

The possibility that negative potassium balance may occur in critically ill preterm neonates is suggested by factors such as the usual provision of minimal potassium intake, increased plasma aldosterone concentrations, increased prostaglandin synthesis, and the frequent use of diuretic agents. In order to assess the relationship between potassium balance and renal prostaglandins, nine infants with respiratory distress syndrome (mean birth weight 1,264 g, mean gestational age 30.6 weeks) were studied sequentially with timed-urine collections during the first four postnatal days and values were compared with those of 18 preterm infants without respiratory distress syndrome. Mean plasma potassium concentrations decreased significantly from 4.87 ± 0.19 mEq/L (mean ± SEM) on day 1 to 3.83 ± 0.18 mEq/L on day 4, (P &amp;lt; 0.05), and cumulative potassium balance was -4.07 ± 0.95 mEq/kg or 10% of estimated total body potassium. Urinary excretion of prostaglandin E, on day 1 in infants with respiratory distress syndrome was significantly greater than in those without respiratory distress syndrome (22.0 ± 4.9 v 8.3 ± 1.6 ng/mg of creatinine) and varied directly with urinary potassium excretion (r = .66, P &amp;lt; .001). These studies suggest that consideration be given to the importance of providing sufficient potassium to prevent hypokalemia in the stressed preterm infant and that pharmacologic agents that alter prostaglandins or potassium excretion should be used with caution.

Adrenocorticotropin-mediated effect of metoclopramide on plasma aldosterone in man.

Five healthy adult men were given metoclopramide (10 and 20 mg) iv and the effects of L-dopa and dexamethasone on metoclopramide-induced increases in plasma aldosterone concentration were determined. Plasma PRL, ACTH, and cortisol levels were also measured and the results reported in a previous study. After an injection of 10 mg metoclopramide, aldosterone levels increased significantly. The aldosterone rise was inhibited by L-dopa, but not by dexamethasone. After injecting 20 mg metoclopramide, aldosterone levels increased significantly vs. both the control and the basal level. The aldosterone increase was not inhibited by L-dopa pretreatment, whereas pretreatment with dexamethasone did suppress it. The data suggest that metoclopramide increased aldosterone secretion through an ACTH-dependent (stress mediated) effect in addition to its antidopaminergic adrenal action, simultaneously. There were no significant differences between the ACTH-dependent and dopamine antagonist-mediated aldosterone increases in either the 10- or 20-mg tests. However, the ACTH-dependent aldosterone increase was statistically greater in the 20-mg test than in the 10-mg test, whereas there was only a slight and not statistically significant difference in the dopamine antagonist-mediated aldosterone increase between the tests. This means that the ACTH-dependent component of the aldosterone secretion is affected by the doubling of the metoclopramide dose, whereas the dopamine antagonist-mediated component is not.

Possible mechanism of action of metoclopramide-induced aldosterone secretion: in vivo and in vitro studies in the sheep.

To define further the mechanism by which metoclopramide, a dopamine antagonist, stimulates aldosterone secretion, seven lambs were injected iv with metoclopramide during a constant infusion of 5% dextrose in water and again during a constant infusion of trimethapan, a ganglionic blocker. In addition, suspensions of adrenal zona glomerulosa cells from the lambs were incubated in vitro in the presence of various concentrations of metoclopramide and known secretagogues. Plasma aldosterone concentrations increased in response to both metoclopramide and trimethaphan. However, during the trimethaphan infusion, no further increase in plasma aldosterone concentrations occurred after metaclopramide injection. In vitro, aldosterone concentrations in the zona glomerulosa cell suspensions increased in the presence of ACTH, potassium, and angiotensin II, but no increase in aldosterone concentration occurred in the presence of metoclopramide. These results suggest that in the sheep, metoclopramide stimulates aldosterone secretion by an indirect mechanism. This mechanism may involve the autonomic nervous system, since ganglionic blockade appeared to abolish the aldosterone response to metoclopramide.

Differing Effects of Metoclopramide and Adrenocorticotropin on Plasma Aldosterone Levels in Glucocorticoid-Suppressible Hyperaldosteronism and Other Forms of Hyperaldosteronism*

To investigate possible dopaminergic effects on aldosterone production, we administered the dopamine antagonist metoclopramide to 11 normal subjects, 8 patients with primary aldosteronism due to adenoma or hyperplasia, and 5 other patients with the glucocorticoid-suppressible form of hyperaldosteronism (GSH). All subjects except for those with GSH responded to metoclopramide with an increase in plasma aldosterone concentration even when endogenous ACTH was suppressed by dexamethasone pretreatment. This increase occurred without apparent mediation of other recognized stimuli for aldosterone secretion. In contrast, the patients with GSH failed to show any aldosterone response while receiving dexamethasone, but demonstrated a rise in plasma aldosterone concentration when dexamethasone was withheld. The responses in the patients with both forms of primary aldosteronism were greater in magnitude than in the normal subjects or in the subjects with GSH when not receiving dexamethasone. These studies, while demonstrating differences between the subtypes of hyperaldosteronism in their responsiveness to metoclopramide, indicate that ACTH or some other factor may exert a permissive effect in GSH for the aldosterone response to metoclopramide. A graded infusion of ACTH revealed a greater aldosterone response in GSH compared to that in the other groups, further suggesting the importance of ACTH in this disorder.

Relation of blood pressure with body and plasma electrolytes in Conn's syndrome.

Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.

A comparison of the effects of angiotensin II infusion and variations in salt intake on plasma aldosterone levels in normal subjects, patients with essential hypertension and patients with hyperaldosteronism

Infusion of angiotensin II into a patient with dexamethasone-suppressible hyperaldosteronism caused a brisk increase in plasma aldosterone concentration. In this behaviour, the patient resembled those patients with idiopathic hyperaldosteronism rather than those with tumorous primary hyperaldosteronism. Sodium depletion of a small group of patients with mild essential hypertension elicited a spectrum of increases in plasma aldosterone levels ranging from zero to normal. Angiotensin II infusion in both sodium replete and deplete states also caused variable aldosterone responses. These results suggest that the derangement of adrenal function in this condition varies continuously in severity.

Response of Thiazide-lnduced Hypokalemia to Amiloride

The effects of amiloride hydrochloride on thiazide-induced hypokalemia were evaluated. In metabolic balance studies, amiloride reversed thiazide-induced urinary potassium loss, restored plasma bicarbonate concentration and pH to pretreatment levels, and produced further increases in aldosterone secretion. Effects of long-term administration of hydrochlorothiazide and an amiloride-hydrochlorothiazide combination were compared in outpatients who had experienced thiazide-induced hypokalemia while receiving oral potassium supplements. After eight weeks, those given hydrochlorothiazide alone had an average serum potassium level of 3.01 +/- 0.08 mEq/L). Those given the amiloride-hydrochlorothiazide combination had an average serum potassium level of 3.75 +/- 0.008 mEq/L, not significantly different from the control value (3.82 +/- 0.08 mEq/L). Both groups had increased plasma aldosterone concentrations and plasma renin activity. The potassium-conserving effect of amiloride persisted with extended therapy.

Primary Aldosteronism: Effects of Inhibition of ACTH and Potassium Administration on Plasma Aldosterone Concentration

The relative roles of ACTH, angiotensin and potassium in influencing aldosterone secretion in primary aldosteronism were assessed by direct or indirect means. In untreated patients with primary aldosteronism caused either by adrenal adenoma or hyperplasia plasma aldosterone and cortisol concentrations fluctuated in unison and dexamethasone reduced both hormones markedly. Only when renin-angiotens in system was greatly activated and plasma potassium normalized by medical treatment was dexamethasone less successful in lowering plasma aldosterone concentration. Potassium infusion of 10, 20 and 30 mEq/hr in patients with adenoma failed to elicit any increase in plasma aldosterone concentration despite significant increases in plasma potassium levels. These results suggest that patients with primary aldosteronism due to adrenal adenoma are relatively more sensitive to small changes in plasma ACTH level than those in plasma angiotensin or potassium levels. In recumbent patients with adrenal hyperplasia ACTH also modulates plasma aldosterone concentration.

Hormonal responses to acute volume changes in anephric subjects

The response of plasma aldosterone and cortisol concentrations to acute volume depletion was studied in 18 chronically anephric subjects and four recently nephrectomized subjects. Volume-depleting hemodialysis and hemodialysis without volume depletion produced insignificant changes in plasma aldosterone concentrations in chronically anephric subjects. Failure of volume depletion to increase plasma aldosterone concentrations in these subjects could not be attributed to reductions in plasma potassium concentrations and was in marked contrast to the effect on plasma cortisol concentrations, which increased significantly during volume depletion. Changes in plasma cortisol concentrations exhibited a negative correlation with changes in diastolic blood pressure (r = -0.712, P less than 0.001) and were shown to correspond to similar changes in plasma ACTH concentrations. Comparable increases in plasma cortisol and ACTH concentrations were also demonstrated in the studies on recently nephrectomized subjects, who, in contrast to chronically anephric subjects, exhibited increases in plasma aldosterone concentrations which were concordant with the changes in plasma cortisol and ACTH concentrations. These findings suggest that plasma aldosterone concentrations are regulated by a volume-sensitive mechanism in recently nephrectomized subjects but not in chronically anephric subjects. We interpret these data as evidence of aldosterone responsiveness to ACTH that persists for a limited time only after removal of the stimulus provided by the renin-angiotensin system. Volume-related changes in plasma cortisol and ACTH concentrations occur in the absence of stimulation by a functioning renin-angiotensin system.