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Aldosterone induces a vascular inflammatory phenotype in the rat heart.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2002 Nov; Vol. 283 (5), pp. H1802-10. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Animals
Blood Pressure
Chemokine CCL2 genetics
Cyclooxygenase 2
Endomyocardial Fibrosis immunology
Endomyocardial Fibrosis pathology
Eplerenone
Gene Expression immunology
Hypertension immunology
Hypertension pathology
Immunohistochemistry
In Situ Hybridization
Intercellular Adhesion Molecule-1 analysis
Isoenzymes genetics
Male
Myocardium chemistry
Myocardium immunology
Myocardium pathology
Osteopontin
Phenotype
Prostaglandin-Endoperoxide Synthases genetics
Rats
Rats, Sprague-Dawley
Sialoglycoproteins analysis
Sialoglycoproteins genetics
Spironolactone pharmacology
Vascular Cell Adhesion Molecule-1 analysis
Vasculitis immunology
Vasculitis pathology
Aldosterone pharmacology
Coronary Vessels drug effects
Coronary Vessels immunology
Spironolactone analogs & derivatives
Vasculitis chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 283
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12384457
- Full Text :
- https://doi.org/10.1152/ajpheart.01096.2001