Aldosterone does not modify gene expression in human endothelial cells

The toxic effects of aldosterone on the vasculature, and in particular on the endothelial layer, have been proposed as having an important role in the cardiovascular pathology observed in mineralocorticoid-excess states. In order to characterize the genomic molecular mechanisms driving the aldosterone-induced endothelial dysfunction, we performed an expression microarray on transcripts obtained from both human umbilical vein endothelial cells and human coronary artery endothelial cells stimulated with 10 - 7 M aldosterone for 18 h. The results were then subjected to qRT-PCR confirmation, also including a group of genes known to be involved in the control of the endothelial function or previously described as regulated by aldosterone. The state of activation of the mineralocorticoid receptor was investigated by means of a luciferase-reporter assay using a plasmid encoding a mineralocorticoid and glucocorticoid-sensitive promoter. Aldosterone did not determine any significant change in gene expression in either cell type both in the microarray and in the qRT-PCR analysis. The luciferase-reporter assay showed no activation of the mineralocorticoid receptor following aldosterone stimulation. The status of nonfunctionality of the mineralocorticoid receptor expressed in cultured human umbilical and coronary artery endothelial cells does not allow aldosterone to modify gene expression and provides evidence against either a beneficial or harmful genomic effect of aldosterone on healthy endothelial cells

Captopril test can give misleading results in patients with suspect primary aldosteronism.

We recently performed a study comparing the SLT with the FST in 100 patients with a positive screening test.4 We report here the results of the captopril test as a confirmatory test in 11 patients in whom SLT and FST displayed concordant results. The captopril test was performed 653 weeks after the previous tests, between 8 am and 10 am, with the subject in the sitting position in a quiet room. Plasma aldosterone concentration and plasma renin activity were measured before and 2 hours after administration of captopril (50 mg). Selection of the patients, diet, therapy, and hormone measurements is described in detail elsewhere.4 Patients were advised to maintain a diet with normal and constant sodium intake (120 mmol of sodium and 60 mmol of potassium per day). All antihypertensive drugs were stopped 653 weeks before the screening test ( 656 weeks for diuretics and 658 weeks for spironolactone). In patients for whom treatment could not be withdrawn for ethical reasons, an \u3b1-blocker (doxazosin) and/or a calcium channel blocker (verapamil) were used for blood pressure control, and the same therapy was maintained throughout the tests. Six patients who had confirmed PA with both FST and SLT underwent a computed tomography scan and adrenal venous sampling. Three patients had bilateral adrenal hyperplasia, and another 3 patients had an aldosterone-producing adenoma. Five patients with both a negative SLT and FST were considered to be essential hypertensive subjects. Five of 6 patients with PA displayed an plasma aldosterone/plasma renin activity ratio postcaptopril >30 ng dL 121/ng mL 121 h 121, but 1 patient with aldosterone-producing adenoma displayed an plasma aldosterone/plasma renin activity ratio postcaptopril 50% of the basal level during the posture test, indicating an angiotensin II\u2013responsive adenoma. By contrast, 3 of 5 patients who displayed a normal suppression of aldosterone after SLT and FST and, therefore, were classified as being affected by essential hypertensives, displayed a plasma aldosterone/plasma renin activity ratio postcaptopril of >30. These patients would have unnecessarily undergone computed tomography scan and adrenal venous sampling relying only on the captopril test, thereby resulting in increased costs and discomfort for the patients. The captopril test has been compared previously with the oral saline load in a group of hypertensive patients with spontaneous hypokalemia and, therefore, at very high risk of PA.5 In fact, 44 of 49 were found to be affected by PA, and for this reason, the authors only discussed the sensitivity and not the specificity of the captopril test. Two aspects should be considered to explain the different findings between our study and the study of Agharazii et al5: first, in our study, only 2 patients (1 aldosterone-producing adenoma and 1 bilateral adrenal hyperplasia) were hypokalemic, whereas Agharazii et al studied only hypokalemic patients and, therefore, could have underestimated the possibility of false-negative results in patients with a mild form of PA; second, a proportion of false-positive patients could have been found by Agharazii et al5 if they had studied a larger population of essential hypertensive subjects. The present data need to be confirmed prospectively in a larger population. However, our findings indicate that, at least in some cases (4 of 11 [36%] in our study), the captopril test was misleading if used as a confirmatory test for the diagnosis of PA. Therefore, in the absence of contraindications such as reduced cardiac or renal function, saline load or FST should be preferred to the captopril test for the confirmatory diagnosis of PA

[Role of aldosterone in the metabolic syndrome].

The purpose of this review is to summarize the current knowledge regarding metabolic syndrome prevalence and features in primary aldosteronism. We will also discuss the link between aldosterone and the different metabolic changes typical of the metabolic syndrome. Hypertensive patients have a high prevalence of obesity, dyslipidemia and hyperglycaemia. These are risk factors for the metabolic syndrome, and are associated with an increased cardiovascular risk profile. In particular, insulin resistance seems to be the major alteration in patients affected by primary aldosteronism. We will then describe the experimental and clinical evidences of the role of aldosterone in the pathogenesis of insulin resistance. Higher rates of cardiovascular events have been recently reported in primary aldosteronism: they could be partly due to the increased prevalence of the metabolic syndrome in this disorder

Aldosterone does not Modify Gene Expression in Human Endothelial Cells.

The toxic effects of aldosterone on the vasculature, and in particular on the endothelial layer, have been proposed as having an important role in the cardiovascular pathology observed in mineralocorticoid-excess states. In order to characterize the genomic molecular mechanisms driving the aldosterone-induced endothelial dysfunction, we performed an expression microarray on transcripts obtained from both human umbilical vein endothelial cells and human coronary artery endothelial cells stimulated with 10 - 7 M aldosterone for 18 h. The results were then subjected to qRT-PCR confirmation, also including a group of genes known to be involved in the control of the endothelial function or previously described as regulated by aldosterone. The state of activation of the mineralocorticoid receptor was investigated by means of a luciferase-reporter assay using a plasmid encoding a mineralocorticoid and glucocorticoid-sensitive promoter. Aldosterone did not determine any significant change in gene expression in either cell type both in the microarray and in the qRT-PCR analysis. The luciferase-reporter assay showed no activation of the mineralocorticoid receptor following aldosterone stimulation. The status of nonfunctionality of the mineralocorticoid receptor expressed in cultured human umbilical and coronary artery endothelial cells does not allow aldosterone to modify gene expression and provides evidence against either a beneficial or harmful genomic effect of aldosterone on healthy endothelial cells

Aldosterone does not modify gene expression in human endothelial cells.

The toxic effects of aldosterone on the vasculature, and in particular on the endothelial layer, have been proposed as having an important role in the cardiovascular pathology observed in mineralocorticoid-excess states. In order to characterize the genomic molecular mechanisms driving the aldosterone-induced endothelial dysfunction, we performed an expression microarray on transcripts obtained from both human umbilical vein endothelial cells and human coronary artery endothelial cells stimulated with 10 - 7 M aldosterone for 18 h. The results were then subjected to qRT-PCR confirmation, also including a group of genes known to be involved in the control of the endothelial function or previously described as regulated by aldosterone. The state of activation of the mineralocorticoid receptor was investigated by means of a luciferase-reporter assay using a plasmid encoding a mineralocorticoid and glucocorticoid-sensitive promoter. Aldosterone did not determine any significant change in gene expression in either cell type both in the microarray and in the qRT-PCR analysis. The luciferase-reporter assay showed no activation of the mineralocorticoid receptor following aldosterone stimulation. The status of nonfunctionality of the mineralocorticoid receptor expressed in cultured human umbilical and coronary artery endothelial cells does not allow aldosterone to modify gene expression and provides evidence against either a beneficial or harmful genomic effect of aldosterone on healthy endothelial cells