Yin Y L, Perret G Y, Nicolas P, Vassy R, Uzzan B, Tod M
Laboratoire de Pharmacologie Clinique et Expérimentale, Faculté de Médecine, Université Paris-Nord, Bobigny, France.
J Cardiovasc Pharmacol. 1992 Apr;19(4):541-5. doi: 10.1097/00005344-199204000-00010.
To assess if the anti-beta-adrenergic effect and the bradycardia induced by amiodarone were mediated by thyroid hormone, we investigated these effects of amiodarone in euthyroid and hypothyroid rats. We studied control rats, thyroidectomized rats, control rats treated with amiodarone (50 mg/kg for 8 days), and thyroidectomized rats treated with amiodarone. At the end of the treatment, free thyroid hormone levels (FT4 and FT3) were determined, and cardiac beta-receptor density (Bmax) and affinity (Kd) were assayed by using (-)-[125I]iodocyanopindolol as radioligand. Resting heart rate (rHR) was also assessed every day in control and thyroidectomized rats, before and after amiodarone. In hypothyroid rats, in which free thyroxine (FT4) was not detectable and free 3,5,3'-triiodothyronine (FT3) was only 16% that of euthyroid rats, Bmax (14.1 +/- 2.5 fmol/mg, n = 7) and rHR (259 +/- 9.7 beats/min, n = 6) were significantly lowered compared with euthyroid rats (Bmax:18.4 +/- 3.4 fmol/mg, n = 7; rHR:277 +/- 4.1 beats/min, n = 5). Amiodarone treatment decreased Bmax (13.6 +/- 2.9 fmol/mg, n = 8) and rHR (252 +/- 5.5 beats/min, n = 5) only in euthyroid rats and did not produce significant cardiac effects in hypothyroid rats. (Values are given as mean +/- SD.) We conclude that a minimum serum thyroid hormone concentration is a necessary condition for amiodarone to produce some of its cardiac effects. An antagonistic reaction to thyroid hormones at the cellular level can be postulated as a mechanism of the cardiac anti-beta-adrenergic action of amiodarone.
为了评估胺碘酮引起的抗β-肾上腺素能效应和心动过缓是否由甲状腺激素介导，我们在甲状腺功能正常和甲状腺功能减退的大鼠中研究了胺碘酮的这些效应。我们研究了对照大鼠、甲状腺切除大鼠、用胺碘酮治疗的对照大鼠（50mg/kg，持续8天）以及用胺碘酮治疗的甲状腺切除大鼠。在治疗结束时，测定游离甲状腺激素水平（FT4和FT3），并使用（-）-[125I]碘氰吲哚洛尔作为放射性配体测定心脏β受体密度（Bmax）和亲和力（Kd）。在对照大鼠和甲状腺切除大鼠中，每天在给予胺碘酮之前和之后评估静息心率（rHR）。在甲状腺功能减退的大鼠中，游离甲状腺素（FT4）无法检测到，游离三碘甲状腺原氨酸（FT3）仅为甲状腺功能正常大鼠的16%，与甲状腺功能正常的大鼠相比，Bmax（14.1±2.5fmol/mg，n=7）和rHR（259±9.7次/分钟，n=6）显著降低（Bmax：18.4±3.4fmol/mg，n=7；rHR：277±4.1次/分钟，n=5）。胺碘酮治疗仅在甲状腺功能正常的大鼠中降低了Bmax（13.6±2.9fmol/mg，n=8）和rHR（252±5.5次/分钟，n=5），而在甲状腺功能减退的大鼠中未产生显著的心脏效应。（数值以平均值±标准差表示。）我们得出结论，最低血清甲状腺激素浓度是胺碘酮产生其部分心脏效应的必要条件。可以假定在细胞水平上对甲状腺激素的拮抗反应是胺碘酮心脏抗β-肾上腺素能作用的一种机制。
