Ameliorating effects of amlodipine on plasma and myocardial catecholamines in BIO 53.58 Syrian hamsters, a model of dilated cardiomyopathy.
Our previous study has shown that the concentrations of norepinephrine, epinephrine and dopamine in the plasma of BIO 53.58 hamsters (a model of dilated cardiomyopathy: DCM) at 18 weeks of age (severe cardiomyopathic stage) were twice those of age-matched F1B control and conversely the myocardial norepinephrine level was decreased. The present study was undertaken to examine the effect of amlodipine on catecholamine concentration, myocardial receptors and histopathological changes in BIO 53.58 hamsters. Oral administration of amlodipine (10 mg/kg/day) for 7 weeks in 11 week-old-BIO 53.58 hamsters brought about marked decreases in the concentrations of norepinephrine, epinephrine and dopamine in the plasma, compared with those in vehicle-treated BIO 53.58 hamsters. This was accompanied by a concomitant increase in the concentration of myocardial catecholamine concentration. In other words, the concentrations of catecholamines in plasma and myocardium of amlodipine administered BIO 53.58 hamsters approximated to the control level in age-matched F1B. In addition, amlodipine administration caused a significant reduction of calcium deposition with a tendency toward a decrease in the myocardial necrosis, and it had little effect on the affinity and number of specific binding for (+)-[3H]PN 200-110, (-)-[125I]iodocyanopindolol (CYP) and [3H]prazosin in the myocardium. In conclusion, the present study shows that administration of amlodipine in BIO 53.58 hamsters may exhibit ameliorating effect on plasma and myocardial catecholamines with a significant reduction of calcium deposition. These data may offer further support for the use of amlodipine in patients with DCM.
Yamada
S
S
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan. yamada@ys7.u-shizuoka-ken.ac.jp
Urayama
A
A
Kimura
R
R
Watanabe
H
H
Ohashi
K
K
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002395:Catecholamines; D017311:Amlodipine