LONG-TERM EFFECTS OF AMIODARONE ON THE TRANSCRIPTION OF T_3-RESPONSIVE GENES IN RATHEARTS~i

摘要

[Aim] The antiarrhythmic mechanisms of amiodarone are not well understood. We investigated the long-term effects of amiodarone on transcription of T_3-responsive genes in the rat hearts in comparison with those of systemic hyperthyroidism and hypothyroidism. [Methods] Wistar rats were assigned to 4 groups and treated for 4 weeks: 1) Non-treatment, 2) systemic hypothyroidism, 3) systemic hyperthyroidism, 4) amiodarone treatment (orally 150 mg/kg daily). ECG recordings, DNA microarray and Northern blot analysis were carried out after each treatment. [Results] Amiodarone treatment, like systemic hypothyroidism, resulted in significant prolongation of RR, QT and QTc intervals. Amiodarone treated group showed similar gene profiles to hypothyroidism by DNA microarray analysis. Amiodarone caused significant decreases in mRNA expression in the heart for myosin heavy chain (MHC) alpha, whereas a significant increase of MHC-beta (n=4). Amiodarone-treated group did not show apparent change with hypothyroidism, in the gene expressions of the liver and the pituitar . Conclusion] Amiodarone causes pothyroid-like changes of electrical properties and transcription of T_3-responsive genes in the heart.