Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components.
OBJECTIVE
In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression.


METHODS
Rats were treated with AM or Dron and the expression of TRalpha 1, TRalpha 2, TRbeta 1 and several tri-iodothyronine (T3)-regulated genes was studied in different parts of the heart, namely the right atrium (RA), left ventricular wall (LVW) and apex.


METHODS
Rats were treated for 14 days with 100 mg/kg body weight AM or Dron. The expression of TRalpha 1, TRalpha 2, TRbeta 1 and T3-regulated genes was studied using real-time PCR and non-radioactive in situ hybridisation.


RESULTS
AM and Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%. In the LVW, AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1. In the apex, AM also increased TRalpha 2. The changes seen in T3-dependent gene expression are reminiscent of foetal reprogramming.


CONCLUSIONS
Taken together, our results indicate that AM and Dron have similar effects on the expression of TR isoforms in the RA, which could partly contribute to their ability to decrease heart rate. On the other hand, the more profound effect of AM appears on TR- and T3-dependent gene expression in the left ventricle suggests foetal reprogramming.
Stoykov
I
I
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.
van Beeren
H C
HC
Moorman
A F M
AF
Christoffels
V M
VM
Wiersinga
W M
WM
Bakker
O
O
D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001835:Body Weight; D000077764:Dronedarone; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000889:Anti-Arrhythmia Agents; D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D000077764:Dronedarone; D000638:Amiodarone; D013974:Thyroxine