Anti-inflammatory effects of eplerenone on viral myocarditis.
OBJECTIVE
Inflammation contributes to increased cardiovascular morbidity and mortality associated with activation of the renin-angiotensin-aldosterone system. The aim of this study was to investigate whether eplerenone, a selective aldosterone receptor antagonist, has anti-inflammatory effects on viral myocarditis.


RESULTS
Four-week-old inbred male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of the encephalomyocarditis (EMC) virus. Mice were fed with standard chow (control) or with chow containing 2.5 mg/kg of eplerenone, starting either on day 0 (inoculation) or day 7. Survival at 28 days was significantly higher in the mice which started eplerenone treatment on day 0 (35 vs. 15% in controls, each n = 40, P < 0.05). The area of myocardial fibrosis on day 28 was significantly smaller in the eplerenone-treated mice than in controls (19.8 +/- 2.6%, n = 14, vs. 33.4 +/- 5.4%, n = 6, mean +/- SEM, P < 0.05). Gene expression of mouse mast cell proteases-4 and -5, matrix metalloproteinase-9, and type I procollagen on day 6 after EMC virus inoculation was significantly decreased in the hearts of eplerenone-treated mice.


CONCLUSIONS
These results suggest that eplerenone has anti-inflammatory effects, and exerts its beneficial effects on viral myocarditis by suppression of genes related to mast cells and cardiac remodelling in the hearts of mice.
Xiao
Jie
J
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Shimada
Miho
M
Liu
Wenling
W
Hu
Dayi
D
Matsumori
Akira
A
D000818:Animals; D018188:Cardiovirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D000077545:Eplerenone; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000473:pathology; D016133:Polymerase Chain Reaction; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D004279:DNA, Viral; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone