Oral administration of candesartan improves the survival of mice with viral myocarditis through modification of cardiac adiponectin expression.
OBJECTIVE
We examined the effects of the angiotensin II receptor type 1 blocker candesartan on myocarditis injury in a murine model of acute myocarditis. We hypothesized that candesartan improves cardiac damage by inducing cardiac expression of adiponectin.


RESULTS
We examined changes in heart failure caused by myocarditis in mice by candesartan based on induction of cardiac adiponectin expression. We intraperitoneally injected encephalomyocarditis virus in C3H mice, then orally administered candesartan (10 mg/kg/day) or vehicle (control). The 7 day survival rate was 18% in the control group, but 60% in the candesartan group. The heart weight/body weight ratio in the candesartan group was significantly lower than in the control group. Circulating adiponectin concentrations on day 7 were significantly higher in the candesartan group compared with the control group (7.91 +/- 0.61 vs. 6.04 +/- 2.26 microg/ml, P < 0.05). Comparative expression of cardiac adiponectin mRNA in the candesartan group was significantly higher than in the control group on day 7 (55.4 +/- 41.3 vs. 5.3 +/- 7.7, P < 0.05). Immunohistochemical staining and in situ hybridization showed that cardiac expression of adiponectin protein and mRNA was present in the candesartan group on day 7.


CONCLUSIONS
Oral administration of candesartan improves survival and decreases myocardial damage in mice with viral myocarditis and induces expression of cardiac adiponectin. The induction of adiponectin might provide cardioprotective effects against acute heart failure due to viral myocarditis.
Saegusa
Seiichiro
S
Department of General Medicine, Kanazawa Medical University, 1-1, Daigaku, Uchinada-Machi, Kahoku-Gun, Ishikawa, Japan.
Fei
Yu
Y
Takahashi
Takashi
T
Sumino
Hiroyuki
H
Moriya
Junji
J
Kawaura
Ken
K
Yamakawa
Jun-ichi
J
Itoh
Tohoru
T
Morimoto
Shigeto
S
Nakahashi
Takeshi
T
Iwai
Kunimitsu
K
Matsumoto
Masayuki
M
Kanda
Tsugiyasu
T
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000821:virology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014777:Virus Diseases / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D015430:Weight Gain / Q000187:drug effects
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; C081643:candesartan