General overview of mineralocorticoid hormone action

Agarwal, M.K.; Mirshahi, Massoud

doi:10.1016/s0163-7258(99)00038-8

Cited by 74 publications

(65 citation statements)

References 456 publications

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“…16 These currents are caused by active sodium channels in apical plasma membrane that are activated by aldosterone either through yet unknown nongenomic mechanisms 17 or through classic genomic mechanisms using intracellular mineralocorticoid receptors. 18 The present data obtained in HUVECs indicate a genomic effect of aldosterone, derived from the fact that the mineralocorticoid receptor antagonist spironolactone blocked the response to the hormone. HUVECs swell in response to the hormone, a phenomenon inhibited by the sodium channel blocker amiloride.…”

Section: Discussionmentioning

confidence: 56%

Human Endothelium: Target for Aldosterone

et al. 2004

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Abstract-Aldosterone has long been known to control water and electrolyte balance by acting on mineralocorticoid receptors in kidney. However, recent studies demonstrated the presence of these receptors in nonclassical locations, including the cardiovascular system. We tested the hypothesis whether endothelial cells respond to aldosterone with changes in cell volume, a measure for ion-mediated water movement across the cell membrane. By means of atomic force microscopy in fluid, we measured volume of adherent human umbilical venous endothelial cells exposed for 72 hours to 10 nmol/L aldosterone. Over this period of time, cells swell by Ϸ18%. Aldosterone-induced swelling is prevented by 100 nmol/L of the mineralocorticoid receptor antagonist spironolactone, added to the primary endothelial cell culture. Aldosterone-treated cells dramatically shrink when 1 mol/L of the diuretic amiloride is applied. Cells deprived of aldosterone do not respond to amiloride. Our conclusions are: (1) aldosterone leads to sustained cell swelling inhibited by administration of spironolactone or the sodium channel blocker amiloride; (2) cells respond to amiloride after aldosterone exposure; (3) renal diuretics act on endothelial cells; and (4) Key Words: endothelium Ⅲ mineralocorticoids T he kidney is known to be the major target for aldosterone, a mineralocorticoid hormone synthesized in the adrenal cortex that acts on electrolyte transport in the distal nephron. 1 However, there is strong evidence that this hormone is also synthesized in heart 2 and blood vessels. 3 At these locations, it is regulated by similar mechanisms comparable to the renin-angiotensin aldosterone system. 4,5 Because of the fact that aldosterone acts on cardiomyocytes, cardiac fibroblasts, and endothelial cells, this hormone plays a major role in the development of heart failure, myocardial fibrosis, and endothelial dysfunction. 6 Moreover, there is much interest in the possibility of the use of aldosterone receptor blockade in patients to diminish pathological effects that can be produced by this hormone. 7 A study applying atomic force microscopy (AFM) on living aortic endothelial cells showed transient cell swelling that occurred over minutes and that was prevented by a high dose of amiloride known to inhibit plasma membrane Na ϩ /H ϩ exchange. 8 Although the underlying mechanism and its physiological relevance were still unclear, attention was placed on data suggesting that endothelial cells not only synthesize aldosterone 3 but also express mineralocorticoid receptors 9 and the epithelial sodium channel. 10 In a recent article, we applied cariporide, a specific Na ϩ /H ϩ exchange inhibitor, to human umbilical venous endothelial cells (HUVECs). 11 To our surprise, we found that the specific Na ϩ /H ϩ exchange inhibitor did not prevent aldosterone-induced cell swelling, whereas, in contrast, a low dose of amiloride known to block plasma membrane sodium channels was most effective. Taken together, these observations indicated that aldosterone triggers the "c...

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Section: Discussionmentioning

confidence: 56%

Human Endothelium: Target for Aldosterone

et al. 2004

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“…These data support the idea that the the membrane-bound sodium channel could well be induced by transcription regulation via the MCR in the nucleocytoplasmic compartment. 14 In future, this technique may be fruitfully employed to assess the localization of various classes of steroid hormone receptors ln health and disease.…”

Section: Data Inmentioning

confidence: 99%

“…The 10 m marker is shown in the 16th sequence of the series. In the dividing cell, the ASSC was centered around the membrane separating the mother and the daughter cells (sequences [6][7][8][9][10][11][12][13][14].…”

Section: Figurementioning

confidence: 99%

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Demonstration of the mineralocorticoid hormone receptor and action in human leukemic cell lines

Mirshahi

Golestaneh

et al. 2000

Leukemia

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We studied the expression of the mineralocorticoid receptor (MCR), and of the amiloride-sensitive sodium channel (ASSC) regulated by the MCR, in human leukemic cell lines. Cell extracts from TF1 (proerythroblastic), HEL (human erythroblastic leukemia) and U937 (myeloblastic) cell line were positive for the ASSC, as a 82 kDa band in Western blots developed with the aid of a polyclonal antibody raised against the peptide QGLGKGDKREEQGL, corresponding to the region 44-58 of the ␣ subunit of the epithelial sodium channel (ENaC) cloned from rat colon, linked to KLH. The polyclonal antibody against the MCR revealed a single band of about 102 kDa in extracts from HEL and TF1 cells. The immunofluorescent labelling of the MCR in all cell lines showed a nucleocytoplasmic localization of the receptor but the ASSC was exclusively membrane-bound and these results were confirmed by confocal microscopy. The expression of the MCR in the HEL cells was evident as a predicted band of 843 bp (234 amino acids) in electrophoresis of the PCR product obtained after total RNA had been reverse transcribed and then amplified using the primers 5′-AGGCTAC-CACAGTCTCCCTG-3′ and 5′-GCAGTGTAAAATCTCCAGTC-3′ (sense and antisense, respectively). The ENaC was similarly evident with the aid of the primers 5′-CTGCCTTTATG GATGATGGT-3′ (sense) and 5′-GTTCAGCTCGAAGAAGA-3′ (antisense) as a predicted band of 520 bp. In both cases, 100% identity was observed between the sequences of the PCR products compared to those from known human sources. The multiplication of the HEL cells was influenced by antagonists (RU 26752, ZK 91587) targeted for specificity to the MCR and this was selectively reversed by the natural hormone aldosterone. These steroids also provoked chromatin condensation in the HEL population. These permit new and novel possibilities to understand the pathobiology of human leukemia and to delineate sodium-water homeostasis in nonepithelial cells. Leukemia (2000) 14, 1097-1104.

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“…L os mineralocorticoides, cuyo principal referente es la aldosterona, se unen con gran afinidad al receptor de mineralocorticoides (MR) y estimulan la reabsorción renal de sodio 1,2 . Al unirse con su ligando, el MR transloca desde el citoplasma al núcleo donde el complejo esteroide-receptor se une a elementos de respuesta (MRE) en el ADN, regulando la transcripción de diversos genes entre los que figuran los del canal renal de sodio y de la bomba sodio-potasio ATPasa que producen a su vez un aumento del transporte tubular de sodio y agua 3,4 .…”

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