Aldosterone induces a vascular inflammatory phenotype in the rat heart.
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.
Rocha
Ricardo
R
Division of Cardiovascular and Metabolic Diseases, Pharmacia Corporation, Skokie, IL 60077, USA.
Rudolph
Amy E
AE
Frierdich
Gregory E
GE
Nachowiak
Denise A
DA
Kekec
Beverly K
BK
Blomme
Eric A G
EA
McMahon
Ellen G
EG
Delyani
John A
JA
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000235:genetics; D003331:Coronary Vessels / Q000187:drug effects* / Q000276:immunology*; D051546:Cyclooxygenase 2; D004719:Endomyocardial Fibrosis / Q000276:immunology / Q000473:pathology; D000077545:Eplerenone; D015870:Gene Expression / Q000276:immunology; D006973:Hypertension / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D053495:Osteopontin; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D014657:Vasculitis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology
D018932:Chemokine CCL2; D007527:Isoenzymes; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D019010:Vascular Cell Adhesion Molecule-1; D053495:Osteopontin; D018799:Intercellular Adhesion Molecule-1; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases