The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes.
Aldosterone binds to the mineralocorticoid receptor (MR) and exerts pleiotropic effects beyond enhancing renal sodium reabsorption. Excessive mineralocorticoid signaling is deleterious during the evolution of cardiac failure, as evidenced by the benefits provided by adding MR antagonists (MRA) to st...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3767808?pdf=render |
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| author | Basile Gravez Antoine Tarjus Ruben Jimenez-Canino Soumaya El Moghrabi Smail Messaoudi Diego Alvarez de la Rosa Frederic Jaisser |
| author_facet | Basile Gravez Antoine Tarjus Ruben Jimenez-Canino Soumaya El Moghrabi Smail Messaoudi Diego Alvarez de la Rosa Frederic Jaisser |
| author_sort | Basile Gravez |
| collection | DOAJ |
| description | Aldosterone binds to the mineralocorticoid receptor (MR) and exerts pleiotropic effects beyond enhancing renal sodium reabsorption. Excessive mineralocorticoid signaling is deleterious during the evolution of cardiac failure, as evidenced by the benefits provided by adding MR antagonists (MRA) to standard care in humans. In animal models of cardiovascular diseases, MRA reduce cardiac fibrosis. Interestingly diuretics such as torasemide also appear efficient to improve cardiovascular morbidity and mortality, through several mechanisms. Among them, it has been suggested that torasemide could block aldosterone binding to the MR. To evaluate whether torasemide acts as a MRA in cardiomyocytes, we compared its effects with a classic MRA such as spironolactone. We monitored ligand-induced nuclear translocation of MR-GFP and MR transactivation activity in the cardiac-like cell line H9C2 using a reporter gene assay and known endogenous aldosterone-regulated cardiac genes. Torasemide did not modify MR nuclear translocation. Aldosterone-induced MR transactivation activity was reduced by the MRA spironolactone, not by torasemide. Spironolactone blocked the induction by aldosterone of endogenous MR-responsive genes (Sgk-1, PAI-1, Orosomucoid-1, Rgs-2, Serpina-3, Tenascin-X), while torasemide was ineffective. These results show that torasemide is not an MR antagonist; its association with MRA in heart failure may however be beneficial, through actions on complementary pathways. |
| first_indexed | 2024-04-13T01:36:15Z |
| format | Article |
| id | doaj.art-46f7d778118448d9b3b6bfff34848bb0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T01:36:15Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-46f7d778118448d9b3b6bfff34848bb02022-12-22T03:08:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7373710.1371/journal.pone.0073737The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes.Basile GravezAntoine TarjusRuben Jimenez-CaninoSoumaya El MoghrabiSmail MessaoudiDiego Alvarez de la RosaFrederic JaisserAldosterone binds to the mineralocorticoid receptor (MR) and exerts pleiotropic effects beyond enhancing renal sodium reabsorption. Excessive mineralocorticoid signaling is deleterious during the evolution of cardiac failure, as evidenced by the benefits provided by adding MR antagonists (MRA) to standard care in humans. In animal models of cardiovascular diseases, MRA reduce cardiac fibrosis. Interestingly diuretics such as torasemide also appear efficient to improve cardiovascular morbidity and mortality, through several mechanisms. Among them, it has been suggested that torasemide could block aldosterone binding to the MR. To evaluate whether torasemide acts as a MRA in cardiomyocytes, we compared its effects with a classic MRA such as spironolactone. We monitored ligand-induced nuclear translocation of MR-GFP and MR transactivation activity in the cardiac-like cell line H9C2 using a reporter gene assay and known endogenous aldosterone-regulated cardiac genes. Torasemide did not modify MR nuclear translocation. Aldosterone-induced MR transactivation activity was reduced by the MRA spironolactone, not by torasemide. Spironolactone blocked the induction by aldosterone of endogenous MR-responsive genes (Sgk-1, PAI-1, Orosomucoid-1, Rgs-2, Serpina-3, Tenascin-X), while torasemide was ineffective. These results show that torasemide is not an MR antagonist; its association with MRA in heart failure may however be beneficial, through actions on complementary pathways.http://europepmc.org/articles/PMC3767808?pdf=render |
| spellingShingle | Basile Gravez Antoine Tarjus Ruben Jimenez-Canino Soumaya El Moghrabi Smail Messaoudi Diego Alvarez de la Rosa Frederic Jaisser The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. PLoS ONE |
| title | The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. |
| title_full | The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. |
| title_fullStr | The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. |
| title_full_unstemmed | The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. |
| title_short | The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. |
| title_sort | diuretic torasemide does not prevent aldosterone mediated mineralocorticoid receptor activation in cardiomyocytes |
| url | http://europepmc.org/articles/PMC3767808?pdf=render |
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