Improvement in the histopathology of hearts from cardiomyopathic BIO TO-2 hamsters following long-term administration of amlodipine and cilnidipine.
The effect of long-term administration of amlodipine and cilnidipine was examined on the histopathology and 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in the left ventricle of BIO TO-2 hamsters, a model of dilated cardiomyopathy (DCM). Oral administration of amlodipine (3 and 10 mg/kg/d, 19 weeks) in 7 week-old BIO TO-2 hamsters produced a significant reduction in calcium deposition and necrosis with little change in the cavity area and fibrosis. A reduction of calcium deposition and necrosis in the myocardium of BIO TO-2 hamsters was also seen following similar administration of cilnidipine (10 mg/kg/d). The long-term administration of amlodipine (3 and 10 mg/kg/d) caused a significant increase (36.6 and 21.7%, respectively) in the Bmax for specific (+)-[3H]PN 200-110 binding in the myocardium from BIO TO-2 hamsters, compared with that in control hamsters. In conclusion, the present study has shown that long-term administration of amlodipine and cilnidipine improves calcium deposition and necrosis in the myocardium from BIO TO-2 hamsters. Thus, these data suggest that both agents may be effective pharmacological treatments of DCM.
Urayama
A
A
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Yamada
S
S
Hirano
K
K
Kimura
R
R
Watanabe
H
H
Ohashi
K
K
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D017849:Animals, Inbred Strains; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D006224:Cricetinae; D004095:Dihydropyridines / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D017311:Amlodipine; C065927:cilnidipine