Comparative effects of losartan, captopril, and enalapril on murine acute myocarditis due to encephalomyocarditis virus.
Losartan, a recently developed nonpeptide angiotensin II (AII) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation. The angiotensin-converting enzyme inhibitors (ACEI) captopril and enalapril were also administered in the same manner to compare the therapeutic effects of these three drugs on the degree of myocarditis, acute heart failure, and left ventricular (LV) hypertrophy. Heart weight and the heart weight/body weight ratio were reduced by losartan (60 mg/kg/day) and captopril (7.5 mg/kg/day), but not by enalapril (1 mg/kg/day). LV wall thickness and cavity dimension were decreased in the losartan and captopril groups. Captopril reduced both myocardial necrosis and inflammation, whereas enalapril reduced myocardial necrosis but not inflammation. However, none of the studied losartan doses (1.2, 12, 60 mg/kg/day) influenced myocardial necrosis and inflammation resulting from viral infection. Thus, specific blockade of AII is beneficial in congestive heart failure (CHF) and LV hypertrophy but is not effective in viral-evoked inflammation and injury.
Araki
M
M
Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kanda
T
T
Imai
S
S
Suzuki
T
T
Murata
K
K
Kobayashi
I
I
D000208:Acute Disease; D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018188:Cardiovirus Infections / Q000188:drug therapy* / Q000401:mortality; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004686:Encephalomyocarditis virus / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D019808:Losartan; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000188:drug therapy* / Q000401:mortality; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013810:Therapeutic Equivalency
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D004656:Enalapril; D002216:Captopril; D019808:Losartan