Ameliorating effects of amlodipine on plasma and myocardial catecholaminesin BIO 53.58 Syrian hamsters, a model of dilated cardiomyopathy

Our previous study has shown that the concentrations of norepinephrine, epi nephrine and dopamine in the plasma of BIO 53.58 hamsters (a model of dilat ed cardiomyopathy: DCM) at 18 weeks of age (severe cardiomyopathic stage) w ere twice those of age-matched FIB control and conversely the myocardial no repinephrine level was decreased. The present study was undertaken to exami ne the effect of amlodipine on catecholamine concentration, myocardial rece ptors and histopathological changes in BIO 53.58 hamsters, Oral administrat ion of amlodipine (10 mg/kg/day) for 7 weeks in 11 week-old-BIO 53.58 hamst ers brought about marked decreases in the concentrations of norepinephrine, epinephrine and dopamine in the plasma, compared with those in vehicle-tre ated 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 amlodipi ne administered BIO 53.58 hamsters approximated to the control level in age -matched F1B. In addition, amlodipine administration caused a significant r eduction of calcium deposition with a tendency toward a decrease in the myo cardial necrosis, and it had little effect on the affinity and number of sp ecific binding for (+)-[H-3]PN 200-110, (-)-[I-125]iodocyanopindolol (CYP) and [H-3]prazosin in the myocardium. In conclusion, the present study shows that administration of amlodipine in BIO 53.58 hamsters may exhibit amelio rating effect on plasma and myocardial catecholamines with a significant re duction of calcium deposition. These data may offer further support for the use of amlodipine in patients with DCM, (C) 2000 Elsevier Science Inc. All rights reserved.