Thyroid hormone alpha(1) and beta(1) receptor mRNA are downregulated by amiodarone in mouse myocardium

Amiodarone, a powerful antiarrhythmic drug, may exert its effect by antagon ism of the thyroid hormone, probably at the receptor level. The aim of this study was to investigate whether amiodarone affects the levels of thyroid hormone receptor (TR) messenger RNA (mRNA) subtypes in mouse hearts. Mice w ere treated with 10, 25, and 50 mg/kg body weight (BW) amiodarone or vehicl e (propyleneglycol) intraperitoneally, daily for 14 days. The heart rate do se-dependently decreased in the 25 mg/kg BW (p < 0.05) and 50 mg/kg BW (p < 0.005) amiodarone-treated mice compared with control. Serum T-3 levels wer e significantly decreased by 25% (4.2 +/- 0.7 pM) in the 50 mg/kg BW amioda rone group in comparison to control (5.6 +/- 1.4 pM; p < 0.05). The serum T -4 levels were 1.3 times higher in 50 mg/kg BW amiodarone-treated mice (13. 2 +/- 1.6 pM) compared with the control(10.3 +/- 1.3 pM; p < 0.005). Determ ination of TR alpha(1), alpha(2), beta(1), and beta(2) mRNA in the heart we re performed by reverse transcriptase-polymerase chain reaction (RT-PCR)/en zyme-linked immunosorbent assay (ELISA). Both in treated and untreated mice , TR alpha(2) mRNA had the highest density in mouse heart, whereas TR beta( 2) mRNA had the lowest density. Amiodarone dose-dependently downregulated t he levels of TR alpha(1) and beta(1) mRNA in comparison to the control. The re were, however, no differences in the TR alpha(2) and TR beta(2) mRNA lev els in the mice heart treated with different doses of amiodarone in compari son with the control group. In conclusion, this study shows that amiodarone subtype selectively downregulates the TR mRNA levels in mouse myocardium i n a dose-dependent manner. These results support a thyroid hormone-dependen t action of amiodarone.