| Nongenomic effects of aldosterone in the human heart: interaction with angiotensin II. | |
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MedLine Citation:
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PMID: 16144984 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aldosterone exerts rapid "nongenomic" effects in various nonrenal tissues. Here, we investigated whether such effects occur in the human heart. Trabeculae and coronary arteries obtained from 57 heart valve donors (25 males; 32 females; 17 to 66 years of age) were mounted in organ baths. Aldosterone decreased contractility in atrial and ventricular trabeculae by maximally 34+/-3% and 15+/-4%, respectively, within 5 to 15 minutes after its application. The protein kinase C (PKC) inhibitor chelerythrine chloride, but not the mineralocorticoid receptor antagonists spironolactone and eplerenone, blocked this effect. Aldosterone also relaxed trabeculae that were prestimulated with angiotensin II (Ang II), and its negative inotropic effects were mimicked by hydrocortisone (at 10-fold lower potency) but not 17beta-estradiol. Aldosterone concentrations required to reduce inotropy were present in failing but not in normal human hearts. Previous exposure of coronary arteries to 1 micromol/L aldosterone or 17beta-estradiol (but not hydrocortisone) doubled the maximum contractile response (Emax) to Ang II. DeltaEmax correlated with extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (P<0.01). Spironolactone and eplerenone did not block the potentiating effect of aldosterone. Studies in porcine renal arteries showed that potentiation also occurred at pmol/L aldosterone levels but not at 17beta-estradiol levels <1 micromol/L. Aldosterone did not potentiate the alpha1-adrenoceptor agonist phenylephrine. In conclusion, aldosterone induces a negative inotropic response in human trabeculae (thereby antagonizing the positive inotropic actions of Ang II) and potentiates the vasoconstrictor effect of Ang II in coronary arteries. These effects are specific and involve PKC and ERK 1/2, respectively. Furthermore, they occur in a nongenomic manner, and require pathological aldosterone concentrations. |
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Authors:
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Wenxia Chai; Ingrid M Garrelds; René de Vries; Wendy W Batenburg; Jorge P van Kats; A H Jan Danser |
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Publication Detail:
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Type: In Vitro; Journal Article Date: 2005-09-06 |
Journal Detail:
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Title: Hypertension Volume: 46 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-30 Completed Date: 2005-12-15 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 701-6 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Erasmus MC, 3015 GE Rotterdam, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aldosterone / administration & dosage, metabolism, pharmacology* Angiotensin II / administration & dosage, pharmacology* Animals Cardiac Output, Low / metabolism Coronary Vessels / drug effects Dose-Response Relationship, Drug Drug Synergism Estradiol / pharmacology Extracellular Signal-Regulated MAP Kinases / metabolism Female Heart / drug effects*, physiology Humans Hydrocortisone / pharmacology Male Middle Aged Myocardial Contraction / drug effects Myocardium / metabolism* Protein Kinase C / metabolism Renal Artery / drug effects Swine Vasoconstriction / drug effects Vasoconstrictor Agents / administration & dosage, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II; 50-23-7/Hydrocortisone; 50-28-2/Estradiol; 52-39-1/Aldosterone; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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