Aldosterone Inhibits Inducible Nitric Oxide Synthase in Neonatal Rat Cardiomyocytes
| Autor: | Tae-Yon Chun, J. Howard Pratt, Laura J. Bloem |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Nitric Oxide Synthase Type II Spironolactone Nitric Oxide Dexamethasone Nitric oxide Rats Sprague-Dawley Transforming Growth Factor beta1 chemistry.chemical_compound Endocrinology Mineralocorticoid receptor Transforming Growth Factor beta Fibrosis Internal medicine medicine Animals Myocytes Cardiac RNA Messenger Aldosterone Glucocorticoids Cells Cultured Mineralocorticoid Receptor Antagonists Dose-Response Relationship Drug biology business.industry medicine.disease Rats Nitric oxide synthase Animals Newborn Gene Expression Regulation chemistry Mineralocorticoid biology.protein Nitric Oxide Synthase business Protein Processing Post-Translational medicine.drug |
| Zdroj: | Endocrinology. 144:1712-1717 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | In studies of animals, increases in aldosterone are associated with myocardial necrosis and fibrosis, and treatment with spironolactone, an antagonist of aldosterone, improved clinical outcomes in patients with heart failure. In the present study, we explored nitric oxide (NO), a signaling molecule involved in cardiac function, as a potential mediator of aldosterone's effects on the heart. Levels of both inducible NO synthase (iNOS) and NO from isolated rat neonatal cardiomyocytes pretreated with IL-1 were found to be decreased with exposure to aldosterone or dexamethasone in a dose-dependent manner. Spironolactone increased iNOS expression and prevented inhibition by aldosterone, consistent with a mineralocorticoid receptor-mediated mechanism for iNOS down-regulation. Aldosterone had no effect on iNOS mRNA levels, indicating a posttranscriptional mechanism for the inhibition of iNOS. Neutralization of TGF-beta 1 using a specific antibody reversed aldosterone-dependent iNOS and NO down-regulation. In summary, aldosterone inhibited IL-1-induced iNOS expression posttranscriptionally by a TGF-beta -dependent mechanism. The decrease in NO synthesis could have relevance to known cardiac effects of aldosterone. |
| Databáze: | OpenAIRE |
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