Hypothyroid-like effect of amiodarone in the ventricular myocardium of the rat.
Due to the similar electrophysiological effects of amiodarone and hypothyroidism in the myocardium, the induction of a local hypothyroid state has been proposed as the mechanism of action of amiodarone. To examine this hypothesis we have studied the influence of amiodarone on the distribution of ventricular isomyosins--a sensitive parameter of the thyroid state in the rat heart--and the effects of amiodarone on 3,5,3'-triiodothyronine (T3) myocardial nuclear receptor binding in vivo. Amiodarone induced a dosage-dependent redistribution of isomyosins similar to hypothyroidism, while simultaneously inducing a low T3 syndrome at the higher dose level. In hypothyroid rats, which were pretreated with amiodarone, substitution of T3 (2 micrograms/100 g) led to a complete reversal of the myosin pattern not differing from control hypothyroid rats which were only given T3; the effect of T3 (0.5 microgram/100 g) was however partially inhibited by amiodarone. Nuclear receptor binding of T3 determined in hypothyroid rats in vivo was unaffected by amiodarone. We conclude that amiodarone induces a hypothyroid-like state in the ventricular myocardium of rats by inhibiting the action of T3--an effect which cannot be attributed to an antagonism at the T3 nuclear receptor level.
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D013956:Antithyroid Agents; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007037:Hypothyroidism / Q000139:chemically induced*; D008297:Male; D009206:Myocardium / Q000032:analysis; D009218:Myosins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000187:drug effects
D013956:Antithyroid Agents; D011988:Receptors, Thyroid Hormone; D009218:Myosins; D000638:Amiodarone