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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin "essential" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.
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PMID:Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states. 18 23

The presence of endothelin (ET) in tumor tissue and plasma of patients with pheochromocytoma was studied by radioimmunoassay. Immunoreactive (ir-) ET concentrations in 12 pheochromocytomas ranged from 66 to 253 fmol per gram wet tissue (gwt) (146 +/- 20 fmol/gwt, mean +/- SEM). These values were not significantly higher than tissue ir-ET concentrations of two primary aldosteronism (66 and 132 fmol/gwt) and three normal adrenal glands (71-120 fmol/gwt) (0.05 less than p less than 0.1). However, tumor tissue ir-ET concentrations in six of the 12 pheochromocytomas were higher than 132 fmol/gwt (the upper value of the control tissues). Sephadex G-50 column chromatography and reverse-phase high-performance liquid chromatography of pheochromocytoma tumor extracts showed a major peak eluting at an identical position to synthetic ET-1. Plasma ir-ET concentrations of pheochromocytomas (1.4 +/- 0.9 fmol/ml, n = 17) were not significantly different from those of patients with essential hypertension (1.0 +/- 0.7 fmol/ml, n = 20) and normal subjects (1.0 +/- 0.4 fmol/ml, n = 18) (0.05 less than p less than 0.1). This study has shown that high concentrations of ET-1 are present in tumor tissues of 50% of pheochromocytomas.
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PMID:Immunoreactive endothelin in pheochromocytomas. 172 1

We studied the response of atrial natriuretic peptide to the hemodynamic and renin-aldosterone variations occurring in four patients who developed cardiac tamponade, either occurring in idiopathic fashion in one or secondary to metastatic involvement of the pericardium in three. Right atrial pressure, heart rate and arterial blood pressure were monitored and serial blood samples were taken before and over three hours after pericardiocentesis. During cardiac tamponade, normal levels of atrial natriuretic peptide (mean +/- SEM: 54 +/- 7.4 pg/ml) were observed in the plasma despite increased right atrial pressure (23 +/- 3.8 cm H2O) and heart rates (98 +/- 4.4). Removal of pericardial fluid (540 to 1160 ml) was associated at first with a 200% increase in plasma concentrations of atrial natriuretic peptide (108 +/- 8.8 pg/ml; P less than 0.001), then with a gradual decline toward normal levels, simultaneous with the normalization of right atrial pressure and heart rate. Activity of renin and concentrations of aldosterone in the plasma were increased during tamponade and returned gradually to normal after pericardiocentesis (3.8 +/- 0.9 to 1.2 +/- 0.3 ng/ml/h and 20 +/- 4.2 to 9 +/- 3.2 ng/dl, respectively; P less than 0.01). These data confirm that atrial strain, not intracavitary pressure in itself nor heart rate, is the main determinant of the acute release of atrial natriuretic peptide, which is associated with a suppressing effect on the renin-aldosterone system. In addition, our data indicate that secretion of atrial natriuretic peptide during cardiac tamponade is not stimulated by secondary hyperaldosteronism.
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PMID:Atrial strain is the main determinant of release of atrial natriuretic peptide. 214 62

The content and biosynthesis of aldosterone and cortisol were examined and compared in the aldosterone-producing adenomas and adjacent adrenal glands from patients with primary aldosteronism that resulted from solitary, benign adrenocortical tumors (0.8 to 32.3 gm). Histologic examination of the six aldosterone-producing adenomas studied confirmed a predominance of cells resembling zona fasciculata rather than zona glomerulosa, as reported in previous studies. Measurement by radioimmunoassay of the tissue content of steroids preformed in vivo demonstrated that aldosterone was present in concentrations 8 times higher in aldosterone-producing adenomas (1.5 +/- 0.5 micrograms/gm tissue; mean +/- SEM) than in adrenal glands (0.2 +/- 0.06 micrograms/gm tissue). Cortisol concentration in aldosterone-producing adenomas (5.4 +/- 1.4 micrograms/gm tissue) was approximately one third that in adrenal glands (15.8 +/- 6.3 micrograms/gm tissue), but cortisol was by far the major steroid in both types of tissue. In vitro, the most important metabolic product quantitatively from 4-carbon 14-labeled cholesterol incubated with mitochondria plus microsomes and from 4-14C-labeled pregnenolone incubated with tissue slices was cortisol, formed in a time-dependent manner in both types of preparations; cortisol synthesis greatly exceed that of aldosterone in adrenal glands, but even in aldosterone-producing adenomas the formation of cortisol was at least 5 times greater than that of aldosterone. The fasciculata structure and dual biosynthetic capacity of aldosterone producing adenomas for cortisol and aldosterone are interpreted in the light of developing concepts of the roles of adrenocorticotropic hormone and of alterations in the microenvironment of the cell in the zonal differentiation of the normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Content and biosynthesis of cortisol in aldosterone-producing adenomas. 275 1

Plasma levels of atrial natriuretic peptide (ANP) were measured in 9 patients with primary aldosteronism and 41 patients with essential hypertension (class I or II by WHO classification) using a specific and sensitive RIA. The mean plasma ANP concentration in patients with primary aldosteronism (mean +/- SEM, 67.1 +/- 10.8 pg/ml; n = 9) was significantly higher than that in healthy normotensive subjects (37.9 +/- 1.4 pg/ml; n = 108) or patients with essential hypertension (38.5 +/- 2.8 pg/ml; n = 41). During treatment with spironolactone, plasma levels of ANP declined in 6 of the 7 patients with primary aldosteronism, but no change occurred in the remaining patient who had cardiac enlargement of unknown etiology. The mean plasma ANP concentration in patients with essential hypertension, on the other hand, was not significantly different from that in normal subjects. These results indicate that plasma ANP levels are elevated in patients with primary aldosteronism, probably due to volume expansion, whereas no abnormality in ANP secretion exists in patients with uncomplicated essential hypertension.
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PMID:Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension. 294 53

Cells isolated from five aldosterone-producing adenomas were used to study glucocorticoid and aldosterone production in response to ACTH, angiotensin II (A II), and peptides derived from proopiomelanocortin (POMC), viz. the 16K N-terminal fragment (16K) and its derivative, gamma 3MSH and the C-terminal fragment beta-lipotropin (beta LPH) and its derivative beta-endorphin. At concentrations similar to those of ACTH and A II (10(-12)-10(-10) M), 16K, gamma 3MSH, and beta LPH selectively stimulated aldosterone production, which reached levels close to those obtained with A II. ACTH, however, was the most effective stimulant of steroidogenesis. The 16K, gamma 3MSH, and beta LPH peptides potentiated the action of ACTH, particularly in the case of aldosterone production. beta-Endorphin, whether used alone or in association with ACTH, had no effect on steroidogenesis at the dose used (10(-10) M). The principal glucocorticoid products of the adenoma cells were cortisol and corticosterone. The ratios of corticosterone to cortisol (B/F) and aldosterone to corticosterone (A/B) varied considerably from one adenoma to another, both basally and in response to ACTH. Nevertheless, within individual adenomas, the mean B/F ratio induced by ACTH [0.280 +/- 0.013 (+/- SEM)] was significantly larger than that induced by A II (0.127 +/- 0.007; P less than 0.001). By contrast, the A/B ratio in response to ACTH (0.061 +/- 0.003) was significantly smaller than that in response to A II (0.159 +/- 0.010; P less than 0.001). The values obtained with 16K (B/F, 0.106 +/- 0.010; A/B, 0.192 +/- 0.028) and gamma 3MSH (B/F, 0.122 +/- 0.012; A/B, 0.178 +/- 0.020) were close to those obtained with A II. 16K and gamma 3MSH potentiated ACTH's effect on steroidogenesis mainly by increasing the A/B ratio from 0.061 +/- 0.003 for ACTH alone to 0.100 +/- 0.008 for 16K plus ACTH (P less than 0.005) and to 0.092 +/- 0.005 for gamma 3MSH plus ACTH (P less than 0.001). The findings suggest that the stimulation of aldosterone production by 16K and gamma 3MSH in aldosteronoma cells is of the A II type and that these peptides may play a role in the genesis of primary aldosteronism.
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PMID:Effects of proopiomelanocortin peptides and angiotensin II on steroidogenesis in isolated aldosteronoma cells. 299 20

Beta agonist therapy for heart failure has been disappointing, perhaps because of renin induced aldosteronism. To investigate this possibility we measured plasma renin activity (PRA) in 23 patients (17 male, 6 female, age 41-70) with New York Heart Association stage III heart failure due to ischaemic heart disease in a placebo controlled trial over one month. All patients received constant doses of digoxin and diuretics throughout the trial. Compliance was confirmed in all patients by digoxin and prenalterol assay. In a preliminary (dose titration) study of 9 patients there was a progressive, but non-significant rise of mean PRA from 14.8 to 17.6 and 27.7 ng/ml per h with doses of 20, 50 and 100 mg of prenalterol, respectively. After one month of treatment with prenalterol (n = 11), PRA was 12.8 +/- 2.4 (SEM) ng/ml per h which was not significantly different from the initial level of 14.4 +/- 2.3 ng/ml per h (n.s.). The placebo group (n = 12) results were 13.8 +/- 4.2 ng/ml per h at entry and 14.4 +/- 5.2 ng/ml per h at one month (n.s.). These results indicate that PRA is elevated by acute treatment with the partial beta agonist prenalterol but stimulation of renin secretion does not appear to occur with chronic therapy.
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PMID:Effect of the partial beta-agonist prenalterol on plasma renin activity in patients with left ventricular failure. 354 8

Enolase isozymes (alpha enolase and gamma enolase) in the extracts of adrenal tumours (phaeochromocytoma, adenoma of primary aldosteronism and Cushing's syndrome, and neurinoma) were determined by means of enzyme immunoassay systems. The mean +/- SEM, respectively, of alpha and gamma enolase levels were 2.5 +/- 0.37 microgram/mg protein and 3.2 +/- 0.69 micrograms/mg protein for 9 phaeochromocytomas, 15.2 +/- 3.1 microgram/mg protein and 0.65 +/- 0.18 microgram/mg protein for three adenomas with primary aldosteronism, 10.8 +/- 3.0 micrograms/mg protein and 0.23 +/- 0.02 micrograms/mg protein for five adenomas causing Cushing's syndrome, and 3.8 +/- 0.88 micrograms/mg protein and 0.30 +/- 0.15 micrograms/mg protein for three neurinomas. Thus, the gamma enolase concentration in the extract of phaeochromocytoma was higher than that of other adrenal tumours. The serum level of gamma enolase was determined in 36 patients with adrenal tumours and 26 normal controls by radioimmunoassay. The mean +/- SEM for gamma enolase level was 5.4 +/- 0.3 ng/ml in normal controls, 9.1 +/- 0.9 ng/ml for 10 patients with phaeochromocytoma, 6.3 +/- 0.3 ng/ml for 11 with primary aldosteronism, 5.5 +/- 0.4 ng/ml for 11 with Cushing's syndrome, and 5.1 +/- 0.7 ng/ml for four with neurinoma. Thus, patients with phaeochromocytoma had a significantly higher serum gamma enolase levels than did those with tumours derived from adrenal cortex and normal controls. In patients with phaeochromocytoma, serum gamma enolase levels showed a significant positive correlation with urinary adrenaline levels (P less than 0.05), and after resection the elevated level of gamma enolase fell significantly (P less than 0.05) and returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determination of enolase isozymes in various adrenal gland tumours. 365 76

The concentrations of unconjugated plasma dopamine (PDA) were studied in patients with various types of hypertension. Catecholamines were extracted from plasma specimens (1.0-3.0 ml) through an Amberlite CG50 (Li+-form) microcolumn and eluted by a magnesium sulfate - ethanol solution. The elute was then desalinated and deproteinized by the ethanol-treated precipitation procedure and dried in a vacuum oven at 25 degrees C. A fraction of catecholamines was assayed with the modified procedures of the COMT-mediated radio-enzymatic method. This assay system was sensitive enough to permit an accurate measurement of PDA as low as 6.0 pg per ml of plasma without any detectable contamination of the conjugated dopamine. The resting levels of PDA were 10.1 +/- 1.0 pg/ml (mean +/- SEM), 9.5 +/- 1.0 and 13.7 +/- 0.6 in patients with borderline hypertension (BH, n = 25), essential hypertension (EH, n = 22) and renovascular hypertension (RVH, n = 8), respectively. The values in EH patients were significantly smaller than those in age-matched normal controls (13.0 +/- 1.4, n = 14, p less than 0.05). Remarkably increased PDA values were observed in patients with pheochromocytoma (76.5 +/- 25.4, n = 9, p less than 0.01). Significantly raised PDA values were also found in patients with primary aldosteronism (PA, 27.8 +/- 9.0, n = 6, p less than 0.05), while their plasma norepinephrine levels (PNE, 169 +/- 39 pg/ml) tended to be lower than those of normal controls (206 +/- 20), showing an apparent dissociation between the values of PDA and PNE. Upright posture for 15 minutes induced a significant rise in PDA (p less than 0.05) in all subjects except PA patients. The postural changes of PDA, however, were invariably smaller than those of PNE (p less than 0.05). The resting values of PDA in normal, BH and EH patients showed a significant negative correlation with their mean arterial pressures (r = -0.301, n = 61, p less than 0.05) and a positive correlation with those of PNE (r = 0.381, p less than 0.01). There was no correlation between PDA and age in any group studied. These findings indicate that PDA might not be only a precursor fraction of neurotransmitters released from the sympathetic nervous system but could also represent a physiological function of the dopaminergic regulatory system. The varied but distinctive features of PDA status in various types of hypertension suggest the possibility that the peripheral dopaminergic mechanisms play an inherent role in the pathogenesis of hypertension.
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PMID:[Plasma dopamine concentrations in various types of hypertension]. 375 30

Plasma aldosterone, 18-hydroxycorticosterone (18-OH-B), 18-hydroxydeoxycorticosterone (18-OH-DOC), corticosterone, cortisol and prolactin levels were determined during an angiotensin II infusion at increasing rates both with and without a simultaneous infusion of dopamine in seven normotensive subjects, in ten patients with essential hypertension, and in ten patients with primary aldosteronism. In a second set of experiments, maximum increases of these plasma levels were determined after metoclopramide (10 mg intravenously) in all subgroups. As compared with the other groups, an exaggerated angiotensin II-induced response of plasma aldosterone and 18-OH-B levels was observed in the five patients with low-renin essential hypertension (LREH) and in five patients with idiopathic hyperaldosteronism (IHA). Dopamine reduced the maximal increase of aldosterone and of 18-OH-B after angiotensin II to 259 +/- 48 (SEM) pg/ml and 511 +/- 152 pg/ml respectively in LREH (without dopamine: 515 +/- 74 and 908 +/- 201 respectively; P less than 0.05), and to 466 +/- 197 and 741 +/- 212 in IHA (without dopamine: 766 +/- 193 and 1264 +/- 337 respectively; P less than 0.05). The maximal increases of plasma aldosterone, 18-OH-B, and prolactin after metoclopramide (10 mg intravenously) were higher (P less than 0.01) in patients with LREH and in patients with primary aldosteronism. Plasma levels of 18-OH-DOC, corticosterone and cortisol were not affected by the stimuli applied. The exaggerated response to metoclopramide as well as to angiotensin II and its reversion only by pharmacological doses of dopamine are consistent with an increased but ineffective dopamine inhibition of aldosterone and 18-OH-B in LREH and IHA.
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PMID:Dopamine reduces aldosterone and 18-hydroxycorticosterone response to angiotensin II in patients with essential low-renin hypertension and idiopathic hyperaldosteronism. 388 12


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