Amiodarone inhibits the 3,5,3'-triiodothyronine-dependent increase of sodium/potassium adenosine triphosphatase activity and concentration in human atrial myocardial tissue.
In animal models the function of the sodium pump (sodium/potassium-adenosine triphosphatase [Na+/K(+)-ATPase]) is enhanced by 3,5,3'-triiodothyronine (T3) and inhibited by the antiarrhythmic agent amio. However, it is still unclear whether the effect of the drug on Na+/K(+)-ATPase depends on the interference with thyroid hormone action. We evaluated the interaction of T3 with amiodarone on Na+/K(+)-ATPase activity and site number in human myocardium. Right atrial slices were cultured with (T3+) and without (T3-) 3 nM T3 in presence and absence of amiodarone at therapeutical dose (1.5 microM). When compared to T3+, T3- preparations showed decreased 3H-ouabain binding (p < 0.004) and lower 20-minute and 45-minute 86Rb-uptake (p < or = 0.004). Amiodarone caused an average 49% reduction of the T3-dependent 3H-ouabain binding and decreased the Western blot signal for the Na+/K(+)-ATPase alpha1 subunit. The drug also inhibited T3-dependent increase in 86Rb-influx at 20 and 45 minutes by 66% and 42%, respectively, without affecting the affinity of the pump for K+. No differences were found in the 3H-ouabain binding and 86Rb-uptake of T3-, T3- amio and T3(+)-amio. In conclusion, T3 stimulates the Na+/K(+)-ATPase in human atrial myocardium by increasing the number of ouabain-binding sites, whereas amiodarone decreases the sodium pump function secondarily to the antagonism with thyroid hormone.
CNR Institute of Clinical Physiology, Pisa, Italy.
Francesca
F
Forini
Giuseppina
G
Nicolini
Silvana
S
Balzan
Gian Michele
GM
Ratto
Bruno
B
Murzi
Vittorio
V
Vanini
Giorgio
G
Iervasi
D000638:Amiodarone / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002675:Child, Preschool; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009924:Organ Culture Techniques / Q000592:standards; D015203:Reproducibility of Results; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D014284:Triiodothyronine; D000254:Sodium-Potassium-Exchanging ATPase; D000638:Amiodarone