Decrease In Plasma Aldosterone Concentration Research Articles

A Decrease in Serum Aldosterone Level is Associated with Maintenance of Sinus Rhythm after Successful Cardioversion of Atrial Fibrillation

The activation of the renin-angiotensin-aldosterone system has been implicated in the progression of atrial structural remodeling during atrial fibrillation (AF). However, consequences of the changes of aldosterone in AF have not been evaluated. This study's aim was to evaluate changes of serum aldosterone concentration after successful cardioversion of persistent AF and to determine the prognostic value of these changes. The prospective, single center study included 45 consecutive patients with nonvalvular persistent AF and preserved left ventricular systolic function, referred for cardioversion. None of the patients were taking aldosterone antagonists. Blood samples for aldosterone measurement were collected twice: 24 hours before and 24 hours after cardioversion. Forty-three patients were successfully converted to sinus rhythm. On the 30th day following cardioversion, 24 patients maintained sinus rhythm (group A), 19 patients relapsed to AF (group B). Serum aldosterone concentration before cardioversion did not differ significantly between both groups (175.6 +/- 112.82 pg/mL vs 125.8 +/- 51.2 pg/mL; P = 0.25). However, in group A serum aldosterone level decreased significantly within 24 hours after cardioversion, from 175.6 +/- 112.8 pg/mL to 101.4 +/- 44.2 pg/mL (P = 0.0034). In group B, the aldosterone level before and after cardioversion did not differ significantly (125.8 +/- 51.2 pg/mL vs 118.2 +/- 59.6 pg/mL; P = 0.68). Logistic regression analysis revealed that a decrease in plasma aldosterone concentration after direct current cardioversion more than 13.2 pg/mL predicted sinus rhythm maintenance in a 30-day follow-up, with 87% sensitivity and 64% specificity. There is a positive correlation between the fall in aldosterone concentration 24 hours after cardioversion and maintenance of sinus rhythm during 30 days of observation.

Effects of trilostane on the pituitary-adrenocortical and renin–aldosterone axis in dogs with pituitary-dependent hypercortisolism

The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during treatment with trilostane were reviewed retrospectively. The correct trilostane dosage in dogs with PDH was based on the resolution of clinical signs and the results of an adrenocorticotropic hormone (ACTH) stimulation test. The mean (+/-SD) dose rate of trilostane to achieve good clinical control was 2.8+/-1.0mg/kg bodyweight. Trilostane treatment resulted in a significant decline in basal plasma cortisol concentrations. The median plasma ACTH concentration (39 pmol/L, range 7-132 pmol/L; n=60) at the optimal trilostane dosage time was significantly higher (P<0.001) than before treatment (13 pmol/L, range 2-102 pmol/L). These values did not overlap with plasma ACTH concentrations (range 212-307 pmol/L) of five PDH dogs with trilostane-induced hypocortisolism. The median cortisol/ACTH ratio in well-controlled dogs (0.23, range 0.03-2.5; n=46) was significantly lower (P<0.001) than before treatment (2.59, range 0.27-13.25). Trilostane treatment resulted in an insignificant decrease in plasma aldosterone concentration (PAC), but the median plasma renin activity (PRA) at the time the trilostane dosage was considered optimal (265 fmol/L/s, range 70-3280 fmol/L/s; n=18) was significantly higher (P<0.001) than prior to treatment (115 fmol/L/s, range 15-1330 fmol/L/s). Similarly, the median PAC/PRA ratio during trilostane treatment (0.16, range 0.003-0.92; n=17) was significantly lower (P<0.001) than before treatment (median 0.44, range 0.04-1.33). Trilostane affected both the hypothalamic-pituitary-adrenocortical and the renin-aldosterone axes. The results also suggested that basal plasma ACTH concentration may be used to detect trilostane overdosage.

Pathophysiology and diagnosis of primary aldosteronism

The pathophysiology of primary aldosteronism still remains unknown. In mRNA and protein levels, overexpression of aldosterone synthase (P-450aldo) is recognized, although abnormalities and defects of DNA and its upper stream have not been detected. Several candidate genes responsible for pathogenesis of primary aldosteronism, such as renin, angiotensin receptor type II, etc., have been proposed, but no decisive genes have been found. A relatively reliable screening for hyperaldosteronism is a determination of the ratio of the plasma aldosterone level to the plasma renin activity. For differentiating several types of aldosteronisms, the simplest test is the response of plasma aldosterone to two hours in an upright posture: plasma aldosterone rises in most patients with idiopathic hyperaldosteronism. In contrast, in cases of autonomous aldosterone-producing tumor, most patients show no response or even a decrease in plasma aldosterone concentration. The size and location of the aldosterone-producing adenoma are determined by using computed tomography.

Age-related impairment of K(+)- and ACTH-stimulated aldosterone secretion by rat adrenal capsules.

It has been suggested that the decrease in plasma aldosterone concentration with advancing age is due to a direct effect of aging on adrenal cortical function. In this study, aldosterone secretion by adrenal capsules from male Fischer 344 rats that were 3-5, 11-13, and 19-21 mo of age was evaluated. Adrenal capsules, comprising the capsule, zona glomerulosa, and small portions of the zona fasciculata-reticularis, were perifused in vitro. Basal aldosterone secretion progressively decreased with aging. In response to concentrations of KCl that ranged from 5.0 to 9.0 mM and to adrenocorticotropic hormone (ACTH) that ranged from 10(-11) to 10(-8) M, threshold sensitivity of adrenal capsules to these secretagogues decreased with aging. Moreover, the magnitude of change in K(+)- and ACTH-stimulated aldosterone secretion and maximal aldosterone response of the adrenal capsules to KCl decreased with aging. Thus it is concluded that aging directly affects basal aldosterone secretion by rat adrenal capsules and that there is an age-related impairment of threshold sensitivity and responsiveness of adrenal capsules to the secretagogues, KCl and ACTH.

Calcitonin gene-related peptide is an inhibitor of aldosterone secretion.

This study examined the effects of calcitonin gene-related peptide (CGRP) on aldosterone secretion both in vivo and in vitro. Intravenous administration of CGRP (0.01 micrograms/kg) in 6 conscious dogs produced a significant decrease in plasma aldosterone concentration from 68 +/- 12 pg/ml to 28 +/- 11 pg/ml (p less than 0.05) despite a mild but significant elevation of plasma renin activity. In an in vitro study using isolated rabbit adrenal glomerulosa cells CGRP reduced the basal aldosterone secretion in a dose-related manner and furthermore 10(-9) M CGRP inhibited the aldosterone secretion stimulated by 10(-8) M angiotensin II. From these results it is suggested that CGRP has an inhibitory effect on aldosterone secretion.

Inhibition of Angiotensin I-Converting Enzyme with S 9490

Summary: S 9780, the diacid form of S 9490, inhibited guinea pig plasma angiotensin-converting enzyme (ACE) by 50% (IC50) at a concentration of 2.4 ± 0.1 nM. A Ki of 1.2 nM was obtained for S 9780 (Dixon-Webb plot) with angiotensin I as a substrate. In rabbits, rats, cats, guinea pigs, and dogs, S 9780 MK 422, S 9490, and MK421 decreased, in a dose-dependent manner, the pressor response to angiotensin I. The rabbit and the rat were the most sensitive species, with ID50 values, respectively, of 2.7 ± 0.4 and 5.9 ± 0.3 μg/kg i.v. for S 9490 and 1.2 ± 0.2 and 2.6 ± 0.8 μg/kg i.v. for S 9780. S 9490 induced a dose-dependent decrease in serum ACE activity in rabbits (0.6-20 μg/kg i.v.) and guinea pigs (10-100 μg/kg i.v.). In conscious rats and dogs S 9490 (0.03-1 mg/kg p.o.) induced a long-lasting inhibition of the angiotensin I-induced pressor response; 40% inhibition was recorded in dogs, 24 h after 1 mg/kg p.o. S 9490 (0.03-0.1 mg/kg i.v.) potentiated the increase in femoral blood flow induced by bradykinin injected into the femoral artery of dogs. In anesthetized dogs, mean blood pressure and heart rate were not changed after sodium restriction, but the cardiac output was markedly decreased. S 9490 (0.1-1 mg/kg i.v.) decreased mean blood pressure both in sodium-restricted and sodium-repleted pentobarbital-anesthetized dogs. However, the lowering effect was more pronounced in sodium-restricted dogs. S 9490 (3 mg/kg p.o.) did not change mean blood pressure in conscious dogs maintained on normal-sodium diet but decreased mean blood pressure in conscious sodium-restricted dogs. Plasma renin activity (PRA) and plasma aldosterone concentration were strongly enhanced in conscious dogs maintained on low-sodium diet. S 9490 (3 mg/kg p.o.) induced a further increase in PRA associated with a decrease in plasma aldosterone concentration. The degree and duration of ACE inhibition appear to exceed those obtained with MK 421 and MK 422.

Maintenance of the antihypertensive efficacy of captopril despite consistent reduction in daily dosage.

1 After a period of 7 +/- 1.4 months of good control of hypertension by thrice daily administration of captopril (85 +/- 9 mg three times a day), captopril was given twice daily and the total dose was progressively reduced to sometimes very low levels in 12 patients. Twice daily administration of captopril 85 +/- 9 mg did not modify blood pressure control. 2 During reduction of captopril dosage to a minimum of 36 +/- 4 mg twice a day, the acute effect of the morning dose of captopril (last dose taken at least 12 hours before study) was assessed. Administration of the morning dose induced a decrease in mean arterial pressure from 112 +/- 4 mm Hg (104 +/- 3 mm Hg during administration of 85 +/- 9 mg) three times a day to 106 +/- 4 mm Hg, an increase in plasma renin activity, and a decrease in plasma aldosterone concentration. 3 These acute effects of captopril suggest that blood pressure was well controlled in the presence of a non-blocked circulating angiotensin-converting-enzyme activity, thus raising the possibility of alternate mechanisms by which captopril reduces arterial pressure. 4 The daily dosage of captopril needed to control hypertension may be reassessed after a certain period of good blood pressure control with 50 to 100 mg captopril three times a day.

Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition.

1 A study was carried out to investigate the possible contribution of prostaglandins in captopril-induced hypotension. 2 Healthy volunteers and patients with essential hypertension were given single oral doses of 25 mg and 50 mg captopril respectively before and after cyclo-oxygenase inhibition with indomethacin. 3 The acute hypotensive effect of captopril was not associated with changes in heart rate. As expected, captopril led to an increase in plasma renin activity, decrease in plasma angiotensin II, and decrease in plasma aldosterone concentration. 4 After acute indomethacin pretreatment the acute hypotensive effect of captopril was significantly blunted in volunteers and in the 14 hypertensive patients. Changes in plasma renin activity and angiotensin II were significantly lower from a lower baseline. 5 Prostaglandins may therefore be mediators of the initial captopril effect. The blunting effect of indomethacin should be taken into account under clinical conditions.

Antihypertensive effect of the oral angiotensin I-converting enzyme inhibitor in long-term treatment of hypertensive patients.

Antihypertensive effect of an orally active angiotensin I-Converting enzyme inhibitor, SQ 14225 (Captopril) was assessed in 18 hypertensive patients, of whom 13 had essential hypertension, 2 had malignant hypertension, 2 had hypertension associated with chronic renal failure, and 1 had renovascular hypertension. Blood pressure decreased markedly not only in patients with high renin levels but also in those with low renin levels. Nevertheless, the magnitude of blood pressure reduction was correlated with the pre-treatment plasma renin activity (r =-0.64, p less than 0.01 systolic, r =- 0.60, p less than 0.05 diastolic). There was a significant correlation between the fall in mean blood pressure and the decrease in plasma aldosterone concentration 3 weeks after treatment (r = 0.64, p less than 0.05). The serum potassium elevated from 4.2 +/- 0.4 to 4.8 +/-0.9 mEq/L (p less than 0.05), and the change correlated inversely with the reduction of plasma aldosterone concentration (r = 0.71, p less than 0.02), while serum sodium slightly decreased from 140-+/- 2 to 138 +/- 3 mEq/L. There was neither finding of orthostatic hypotension nor escape from the antihypertensive effect. These results indicate that chronic inhibition of angiotensin I-converting enzyme with an orally active compound offers an effective and well-tolerated approach to treatment of hypertension.

Primary Aldosteronism

New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion.

Outpatient Screening Tests for Primary Aldosteronism

The assessment of basal plasma aldosterone and renin concentrations, and urinary aldosterone excretion has been compared with their values after a suppressive test employing mineralocorticoid induced volume expansion in five patients with primary aldosteronism and in patients with essential hypertension. Reliance upon measurements of basal plasma aldosterone concentration, plasma renin/aldosterone ratio and urine aldosterone excretion alone proved unsatisfactory for distinguishing patients with primary aldosteronism. However these patients, in contrast to those with essential hypertension, showed elevated values or no decrease in plasma aldosterone concentration following three days treatment with 400 mug fludrocortisone (florinef) daily. It is proposed that the assessment of basal plasma renin activity together with florinef suppression of plasma aldosterone are the most effective and convenient outpatient screening procedures in the diagnosis of primary aldosteronism.