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Title:LONG-TERM EFFECTS OF AMIODARONE ON THE TRANSCRIPTION OF T3-RESPONSIVE GENES IN RAT HEARTS
DOI No:10.1142/9789812702234_0023
Source:ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 97-102)
Author(s):RONGQIAN SHI
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

JONG-KOOK LEE
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

YOKO TAKEUCHI
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

MITSURU HORIBA
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

KENJI YASUI
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

FUKUSHI KAMBE
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

YOSHIHARU MURATA
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

ITSUO KODAMA
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan

Abstract:[Aim] The antiarrhythmic mechanisms of amiodarone are not well understood. We investigated the long-term effects of amiodarone on transcription of T3-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 changes with hypothyroidism, in the gene expressions of the liver and the pituitar [Conclusion] Amiodarone causes hypothyroid-like changes of electrical properties and transcription of T3-responsive genes in the heart.
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