An angiotensin II receptor antagonist reduces myocardial damage in an animal model of myocarditis.
BACKGROUND
Recently, an angiotensin-converting enzyme inhibitor was shown to have a beneficial effect on virus-induced myocardial injury. We investigated the effect of a new angiotensin II type 1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-1H-benz imi dazole-7- carboxylate (TCV-116), in an animal model of viral myocarditis induced by encephalomyocarditis virus.


RESULTS
Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. TCV-116 (in 5% gum arabic) was given 1 day before (1 or 10 mg/kg) or 2 days after virus inoculation (0.3 or 3 mg/kg). Control mice received the vehicle only. All drugs were administered orally on a daily basis, and the animals were killed on day 14. When treatment was started 1 day before inoculation, the survival of mice receiving 10 mg/kg of TCV-116 improved (17 of 20 [85%] versus 14 of 22 [64%] control mice), but the difference was not significant. Heart weight (106 +/- 24 mg versus 133 +/- 33 mg, P < .05), histological scores for myocardial necrosis (1.1 +/- 0.3 versus 2.3 +/- 1.2, P < .01), cellular infiltration (1.4 +/- 0.7 versus 2.6 +/- 1.3, P < .05), and calcification (1.1 +/- 0.3 versus 2.1 +/- 1.1, P < .01) were significantly decreased in mice given TCV-116 at 3 mg/kg compared with the vehicle control mice. The plasma angiotensin II level was significantly higher in infected mice than in noninfected mice (71.8 +/- 30.2 versus 31.8 +/- 22.5 pg/mL, P < .05). TCV-116 did not inhibit viral replication in the heart.


CONCLUSIONS
This study suggests that angiotensin II plays an important pathophysiological role in viral myocarditis. Treatment with TCV-116, an angiotensin II receptor antagonist, had a cardioprotective effect.
Tanaka
A
A
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Matsumori
A
A
Wang
W
W
Sasayama
S
S
D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D018188:Cardiovirus Infections; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D016019:Survival Analysis; D013777:Tetrazoles; D014779:Virus Replication / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; C077793:candesartan cilexetil