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


CONCLUSIONS
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.
Yu
Fei
F
Department of General Medicine, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.
Chen
Rui
R
Takahashi
Takashi
T
Sumino
Hiroyuki
H
Morimoto
Shigeto
S
Nakahashi
Takeshi
T
Iwai
Kunimitsu
K
Matsumoto
Masayuki
M
Kanda
Tsugiyasu
T
D052242:Adiponectin / Q000096:biosynthesis*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D018188:Cardiovirus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004686:Encephalomyocarditis virus / Q000187:drug effects; D005260:Female; D051379:Mice; D008820:Mice, Obese; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
D052242:Adiponectin; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan