| Aldosterone induces a vascular inflammatory phenotype in the rat heart. | |
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MedLine Citation:
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PMID: 12384457 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vascular inflammation was examined as a potential mechanism of aldosterone-mediated myocardial injury in uninephrectomized rats receiving 1% NaCl-0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle, 2) aldosterone infusion (0.75 microg/h), or 3) aldosterone infusion (0.75 microg/h) plus the selective aldosterone blocker eplerenone (100 mg. kg(-1). day(-1)). Aldosterone induced severe hypertension at 4 wk [systolic blood pressure (SBP), 210 +/- 3 mmHg vs. vehicle, 131 +/- 2 mmHg, P < 0.001], which was partially attenuated by eplerenone (SBP, 180 +/- 7 mmHg; P < 0.001 vs. aldosterone alone and vehicle). No significant increases in myocardial interstitial collagen fraction or hydroxyproline concentration were detected throughout the study. However, histopathological analysis of the heart revealed severe coronary inflammatory lesions, which were characterized by monocyte/macrophage infiltration and resulted in focal ischemic and necrotic changes. The histological evidence of coronary lesions was preceded by and associated with the elevation of cyclooxygenase-2 (up to approximately 4-fold), macrophage chemoattractant protein-1 (up to approximately 4-fold), and osteopontin (up to approximately 13-fold) mRNA expression. Eplerenone attenuated proinflammatory molecule expression in the rat heart and subsequent vascular and myocardial damage. Thus aldosterone and salt treatment in uninephrectomized rats led to severe hypertension and the development of a vascular inflammatory phenotype in the heart, which may represent one mechanism by which aldosterone contributes to myocardial disease. |
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Authors:
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Ricardo Rocha; Amy E Rudolph; Gregory E Frierdich; Denise A Nachowiak; Beverly K Kekec; Eric A G Blomme; Ellen G McMahon; John A Delyani |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 283 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-10-17 Completed Date: 2002-11-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1802-10 Citation Subset: IM |
Affiliation:
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Division of Cardiovascular and Metabolic Diseases, Pharmacia Corporation, Skokie, IL 60077, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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pharmacology* Animals Blood Pressure Chemokine CCL2 / genetics Coronary Vessels / drug effects*, immunology* Cyclooxygenase 2 Endomyocardial Fibrosis / immunology, pathology Gene Expression / immunology Hypertension / immunology, pathology Immunohistochemistry In Situ Hybridization Intercellular Adhesion Molecule-1 / analysis Isoenzymes / genetics Male Myocardium / chemistry, immunology, pathology Osteopontin Phenotype Prostaglandin-Endoperoxide Synthases / genetics Rats Rats, Sprague-Dawley Sialoglycoproteins / analysis, genetics Spironolactone / analogs & derivatives*, pharmacology Vascular Cell Adhesion Molecule-1 / analysis Vasculitis / chemically induced*, immunology, pathology |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL2; 0/Isoenzymes; 0/Sialoglycoproteins; 0/Spp1 protein, rat; 0/Vascular Cell Adhesion Molecule-1; 0/eplerenone; 106441-73-0/Osteopontin; 126547-89-5/Intercellular Adhesion Molecule-1; 52-01-7/Spironolactone; 52-39-1/Aldosterone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases |
| Comments/Corrections | |
Comment In:
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Am J Med. 2003 Aug 15;115(3):250
[PMID:
12935835
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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