Effect of ACTH on plasma renin activity, aldosterone level and deoxycorticosterone level in humans (author's transl)]

Plasma aldosterone level (PAL) and deoxycorticosterone level (PDL) were determined in 5 subjects of normal sodium intake and 5 subjects of low sodium intake after the intramuscular administrations of ACTH (Upjohn, Cortrosyn) 40 IU, using radioligand methods. PAL and PDL reached their peaks at one hour after the administrations of ACTH, and then decreased in their normal ranges. Pretreated with the oral administrations of Dexamethasone 2 mg/day for 2 days, these subjects had, when ACTH were injected, such a similiar pattern in PAL and PDL as the peak of one hour and the consecutive falling without the pretreating of Dexamethasone. PAL and PDL of these subjects were not different between normal sodium intake and low sodium intake during the course of the experiment.     

Behavior of the plasma renin activity and aldosterone after salt restriction and upright posture in essential hypertension]

In 100 patients with essential hypertension and 50 healthy subjects the relation between plasma renin activity (PRA) and plasma aldosterone level (Ald) was investigated. PRA as well as plasma aldosterone was estimated a) after a diet with normal sodium content (equals 120 mEq per day) provided for 3 days and after an 8 hrs rest ("L" value of PRA and Ald) and b) after sodium restriction (10 mEq per day) for 3 days and 3-4 hrs ambulation ("A" value of PRA and Ald). Concerning the behaviour of "L"- und "A"-PRA all patients were divided into 4 groups: a) patients with normal, b) rigid, c) low and d) high PRA. Despite differentiated values of PRA in patients of all groups a normal increase of the plasma aldosterone level was stated after sodium restriction in the diet and upright position. Even in 18% of healthy subjects with low PRA a normal increase of Ald after sodium restriction and upright position was observed. These results seem to prove that in patients with low and rigid PRA and in 18% of healthy subjects the renin-angiotensin system is not the main or only regulator of aldosterone secretion.     

Correlations between plasma renin activity, angiotensin II, and aldosterone.

To obtain more information about the relationships of the components of the renin-angiotensin-aldosterone system, we measured plasma renin activity (PRA) and the concentrations of plasma angiotensin II (AII) and aldosterone (PA) in 36 healthy 19-22-yr-old students, both after a night's bed rest and after 2 h of ambulation. The correlations of these parameters were calculated. PRA, AII, and PA were determined by RIAs. The values of AII after rest correlated positively both with PRA (r = 0.80; P less than 0.001) and with PA (r = 0.51; P less than 0.01). AII also showed a good correlation with PRA (r = 0.77; P less than 0.001) and with PA (r = 0.67; P less than 0.01) after ambulation. The latter correlation was higher than that after rest. Positive correlations were also found between the increases in PRA and AII and between AII and PA. Further, a multiple regression analysis was carried out to calculate the regression equations for these parameters. The results support the view that PRA and AII parallel each other in normal physiological circumstances. They also seem to indicate that AII has an important role in the basal as well as in the posture-stimulated secretion of aldosterone in normal man.     

The mechanism of low-renin hypertension: aldosterone response to sodium restriction and upright posture, angiotensin II, ACTH and potassium in patients with hypertension.

Plasma renin activity and aldosterone were measured simultaneously in 67 out-patients with essential hypertension. High aldosterone was more often in patients with high renin, and low levels of aldosterone were usual in those with low and normal renin. In order to study the mechanism by which aldosterone and renin acitvity are suppressed in low-renin hypertension, 25 patients (13 normal-renin hypertensives, 10 low-renin patients including 4 non-responders and two DOC excess hypertensives) were investigated as inpatients. Plasma renin activity, aldosterone and cortisol were determined by the following stimualtions with 3 days of sodium restriction and 2 hours of upright posture, angiotensin II infusion (at a dose which increased 20mmHg of diastolic blood pressure), ACTH administration (rapid i.m. injection of 0.25 mg of alpha 1-24 preparation) and potassium infusion (30 meq of potassium i.v.). Responses of aldosterone in normal-renin hypertensives to all stimulations were 3-5 fold increases from bases line values. Low-renin hypertensives except two of four non-responders showed the responses similar to those in normal-renin patients. The responses of two of the non-responders were similar to those in DOC excess hypertensives who showed reduced responses of aldosterone to some of these stimulations. Thus, it seems that low-renin hypertension is a clinical entity caused by a variety of mechanisms, and the mechanism by which low-renin hypertension is induced is not explained by one factor such as an unknown mineralocorticoid.     

Plasma aldosterone and renin activity in hypopituitarism (author's transl)

Plasma renin activity (P.R.A.) and plasma aldosterone were measured in twelve patients having hypopituitarism. Both mean values of this group were significantly lower than in normal subjects (P.R.A. recumbent: p less than 0.001, upright: p less than 0.001, plasma aldosterone: recumbent: p less than 0.02, upright: p less than 0.005). Hyporeninism is a controversed feature in hypopituitarism. Our preliminary data suggest that it is not directly correlated to ACTH or cortisol deficiency. Nevertheless it may explain the hypoaldosteronism prior reported in such patients.     

Plasma aldosterone response to upright posture and angiotensin II infusion in aldosterone-producing adenoma.

Nineteen patients with primary aldosteronism due to surgically confirmed aldosterone-producing adenoma (APA) were examined to evaluate the response of aldosterone to upright posture and angiotensin II infusion. Upright posture reportedly decreases the plasma aldosterone concentration (PAC) in APA but raises it in idiopathic hyperaldosteronism. However, our findings showed the opposite result, in that the upright posture did not change or raised PAC in 15 of 19 cases (79%). Angiotensin II was infused i.v. at doses from 0.5-2 ng/min.kg body weight in six patients in whom the upright posture raised PAC, but did not raise PAC in all cases. This result supports the assumption that APA is functionally insensitive to angiotensin II. A concomitant rise of ACTH, pretreatment with calcium channel blockade, and other modulating factors may be involved in this PAC rise. Whatever the reason, such a high frequency of patients with increased PAC in APA raises some question about the clinical value of the upright posture test. We believe, then, there is reason to check any interpretation concerning increased PAC in the case of the upright posture test in distinguishing between APA and idiopathic hyperaldosteronism.     

Effect of upright posture on the aldosterone responses to dopamine, metoclopramide, angiotensin II, and adrenocorticotropin

Aldosterone secretion in man is stimulated by potassium (K), ACTH, and angiotensin II (AII) and inhibited by dopamine (DA). In normal sodium-replete supine individuals, aldosterone secretion is under maximum tonic inhibition by DA and is not inhibited further by DA administration. Sodium depletion alters plasma aldosterone responses to secretogogues. Upright posture, another physiological stimulus to aldosterone secretion, recently was demonstrated to sensitize the adrenal cortex to inhibition of aldosterone secretion by a large quantity of DA (4.0 micrograms/kg X min). The effect of upright posture on aldosterone responses to other secretogogues is unknown. In this study, we investigated the effect of upright posture on aldosterone responses to low infusion rates of DA, to the DA antagonist metoclopramide (M) and to AII and ACTH. Fourteen normal men eating a normal sodium diet were studied. In eight, PRA, plasma aldosterone (PAC), plasma cortisol (F), and serum K concentrations were determined after 4 h of upright posture and infusion of vehicle (D5W) or DA at 0.1, 0.4, and 2.0 micrograms/kg X min. Six other normal men were kept supine for 3 h and, on separate days, upright for 3 h and given iv M (10-mg bolus dose), AII (1 and 4 pmol/kg X min for 30 min), and ACTH (20 and 120 mU/h for 30 min). PAC, PRA, F, and K were measured before and after these three secretogogues were administered. In the presence of vehicle, mean PAC increased by 15.1 +/- 4.3 (+/- SEM) ng/dL after 4 h of upright posture. In the presence of DA infused at 0.1, 0.4, and 2.0 micrograms/kg X min, the PAC response to upright posture was decreased to 9.7 +/- 2.5 (P = NS), 7.5 +/- 3.9 (P less than 0.05), and 8.1 +/- 2.0 (P less than 0.05) ng/dL, respectively. This occurred without a decrease in PRA, F, or K. The stimulation of PAC 10 and 20 min after a 10-mg bolus dose of M was 9.6 +/- 3.3 and 9.3 +/- 2.6 ng/dL, respectively, in supine subjects and 8.3 +/- 2.3 and 10.8 +/- 3.4 ng/dL 10 and 20 min after the M dose in upright subjects. The responses of PAC to ACTH and AII also were unchanged after 3 h of upright posture. We conclude that upright posture sensitizes the adrenal cortex to inhibition of aldosterone secretion by DA without affecting other modifiers of aldosterone secretion.(ABSTRACT TRUNCATED AT 400 WORDS)