Long-term effects of amiodarone and its non-iodinated analogue, dronedarone, on the transcription of cardiac sarcoplasmic reticulum Ca(2+)-ATPase gene

Abstract

Antiarrhythmic effects of long-term amiodarone is supposed to be mediated in part by cardio-selective hypothyroidism, but the issue remains controversial. mRNA expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was examined by Northern blot analysis in rats treated with amiodarone (60 mg/kg/day, 4 weeks) or dronedarone (60 mg/kg/day, 4 weeks). SERCA2 mRNA level in ventricular muscle was significantly decreased in hypothyroid rats by 38 +/- 9 percent (p less than 0.05, n = 4), whereas increased in hyperthyroid rats by 39 +/- 19 percent (p less than 0.05, n = 4) compared with control (euthyroid) rats. Amiodarone treatment caused a slight decrease in SERCA2 mRNA (by 20 +/- 13 percent, n = 4), whereas dronedarone treatment caused a slight increase (by 19 +/- 23 percent, 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.