title: In vivo effects of amiodarone on cardiac beta-adrenoceptor density and heart rate require thyroid hormones.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacologie Clinique et Expérimentale, Faculté de Médecine, Université Paris-Nord, Bobigny, France.
authors.forename: Y L
authors.initials: YL
authors.lastname: Yin
authors.forename: G Y
authors.initials: GY
authors.lastname: Perret
authors.forename: P
authors.initials: P
authors.lastname: Nicolas
authors.forename: R
authors.initials: R
authors.lastname: Vassy
authors.forename: B
authors.initials: B
authors.lastname: Uzzan
authors.forename: M
authors.initials: M
authors.lastname: Tod
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D013965:Thyroidectomy; D013974:Thyroxine / Q000097:blood / Q000502:physiology*; D014284:Triiodothyronine / Q000097:blood / Q000502:physiology*
chemical_list: D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D000638:Amiodarone; D013974:Thyroxine