Candesartan improves myocardial damage in obese mice with viral myocarditis and induces cardiac adiponectin.

Abstract

PURPOSE:

To clarify the mechanism of the effects of angiotensin II receptor type 1 antagonist, candesartan, upon cardiac adiponectin in the combination of myocarditis with obesity, we examined obese KKAy mice with acute viral myocarditis treated by candesartan and investigated cardiac adiponectin regulation.

METHODS:

Mice were divided into candesartan early treatment group (Can-early) receiving orally candesartan at daily dose of 10 mg/kg 7 days starting before viral inoculation and then 7 days; candesartan late treatment group (Can-late) or vehicle (Vehicle) receiving candesartan starting simultaneously with viral inoculation and then 7 days. Encephalomyocarditis virus was used to induce the acute viral myocarditis. Differences in myocardial damages, serum adiponectin and myocardial expression of adiponectin, tumor necrosis factor-alpha (TNF-alpha), CCAAT/enhancer binding proteinalpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor-kappaB (NF-kappaB) mRNA among three groups were determined on days 0, 4 and 7 after viral inoculation.

RESULTS:

Mice in Can-early and Can-late groups showed reduced myocardial necrosis and cellular infiltration as compared with those in the Vehicle. On day 4 the circulating adiponectin levels were significantly higher in Can-early than those in Vehicle. Mice in Vehicle had significantly reduced in myocardial adiponectin mRNA after viral myocarditis. Cardiac adiponectin mRNA was significantly higher in Can-early and in Can-late than in Vehicle on days 4 and 7. Cardiac C/EBPalpha in Can-early and Can-early groups was significantly increased on day 4. Myocardial NF-kappaB and TNF-alpha mRNA in Can-early and Can-late groups were significantly reduced on day 7.

CONCLUSION:

Candesartan treatment improved myocardial injury in obese mice with acute viral myocarditis and induced expression of cardiac adiponectin with the induction of C/EBPalpha as well as the reduction of cardiac NF-kappaB and TNF-alpha.

• Authors: Fei Yu, Rui Chen, Takashi Takahashi, Hiroyuki Sumino, Shigeto Morimoto, Takeshi Nakahashi, Kunimitsu Iwai, Masayuki Matsumoto, Tsugiyasu Kanda
• Journal: International journal of cardiology (Int J Cardiol) Vol. 129 Issue 3 Pg. 414-21 (Oct 13 2008) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 18053594 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Benzimidazoles
• Biphenyl Compounds
• Tetrazoles
• candesartan

Topics

• Adiponectin (biosynthesis)
• Animals
• Benzimidazoles (pharmacology, therapeutic use)
• Biphenyl Compounds
• Body Weight (drug effects, physiology)
• Cardiovirus Infections (drug therapy, metabolism, pathology)
• Encephalomyocarditis virus (drug effects)
• Female
• Mice
• Mice, Obese
• Myocarditis (drug therapy, metabolism, pathology)
• Tetrazoles (pharmacology, therapeutic use)