Long-term Effects of Amiodarone and its Non-iodinated Analogue, Dronedarone, on the Transcription of Cardiac Sarcoplasmic Reticulum Ca^ -ATPase Gene

Antiarrhythmic effects of long-term amiodarone is supposed to be mediated in part by cardio-selective hypothyroidism, but the issue remains controversial. We examined mRNA expression of sarcoplasmic reticulum Ca 2 + -ATPase (SERCA2) by Northern blot analysis in rats treated with amiodarone (60mg/kg/day, 4 weeks) or dronedarone (60mg/kg/day, 4 weeks). SERCA2 mRNA level in ventricular muscle was significantly decreased in hypothyroid rats by 38′9% (p<0.05, n=4), whereas increased in hyperthyroid rats by 39′19% (p<0.05, n=4) compared with control (euthyroid) rats. Amiodarone treatment caused a slight decrease in SERCA2 mRNA (by 20′13%, n=4), whereas dronedarone treatment caused a slight increase (by 19′23%, n=3), although the changes did not reach statistical significance. Amiodarone and dronedarone have different effects on the gene transcription of SERCA2 in the heart, suggesting their different thyroid hormone-mediated actions.