Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production.
BACKGROUND
Although calcium channel blockers have not been shown to be beneficial for the treatment of patients with heart failure, a recent clinical trial demonstrated a favorable effect of amlodipine on the survival of patients with heart failure resulting from nonischemic dilated cardiomyopathy. We investigated the effects of amlodipine on a murine model of congestive heart failure induced by the M variant of encephalomyocarditis virus (EMCV).


RESULTS
Four-week-old male DBA/2 mice were inoculated with EMCV and administered amlodipine, diltiazem, or vehicle PO for 2 weeks. The heart weight-to-body weight ratio and the histopathological grades of myocardial lesions were significantly lower and survival was significantly increased in the amlodipine-treated group (P < .01, P < .05, and P < .05, respectively) than in the control group. In vitro, amlodipine added to murine J774A.1 macrophages concomitant with EMCV inhibited nitrite formation in a concentration-dependent manner, but diltiazem did not. Furthermore, NG-monomethyl-L-arginine, an inhibitor of NO synthesis, decreased myocardial lesions significantly in this murine model. Immunohistochemistry revealed that the number of cells stained with antibody against an inducible NO synthase decreased significantly in the amlodipine-treated group compared with that in the control group (P < .01).


CONCLUSIONS
Amlodipine appears to have a protective effect against myocardial injury in this animal model of congestive heart failure. The therapeutic effect of amlodipine may be in part resulting from inhibition of overproduction of NO.
Wang
W Z
WZ
Department of Cardiovascular Medicine, Kyoto University, Japan.
Matsumori
A
A
Yamada
T
T
Shioi
T
T
Okada
I
I
Matsui
S
S
Sato
Y
Y
Suzuki
H
H
Shiota
K
K
Sasayama
S
S
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D018188:Cardiovirus Infections / Q000150:complications; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000302:isolation & purification; D006321:Heart / Q000033:anatomy & histology / Q000821:virology; D006333:Heart Failure / Q000188:drug therapy* / Q000821:virology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000821:virology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009929:Organ Size
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester