L-triiodothyronine acutely increases Ca2+ uptake in the isolated, perfused rat heart. Changes in L-type Ca2+ channels and beta-receptors during short- and long-term hyper- and hypothyroidism.

Acutely administered triiodothyronine (T3) in supraphysiological doses has been shown to exert an acute positive inotropic effect in vivo a few minutes after intravenous administration. To investigate whether this effect could be explained by an acutely increased Ca2+ uptake in the myocardium, an isolated perfused rat heart model ad modum Langendorff was established. The acute stimulative effect of T3 on myocardial Ca2+ uptake was determined indirectly by measuring changes in Ca2+ concentration in the perfusate following coronary perfusion with 45Ca(2+)-containing buffer. Perfusion with T3 gave rise to dose-dependent reductions in perfusate Ca2+ within 20 s. Following 10(-9) and 10(-11) mol/l T3, the effect was small and usually lasted less than 1 min. Perfusion with 10(-6) and 10(-7) mmol/l T3 resulted in a decrease in perfusate Ca2+, which remained stable throughout 4-6 min of observation. Calcium channel blockade with nifedipine prevented the decrease in perfusate Ca2+, suggesting that voltage-operated Ca2+ channels are involved in the increased Ca2+ uptake. A washout period with T3-free buffer re-established the Ca2+ concentration in the perfusate, suggesting that the effect is reversible. Calcium channels have been suggested to be regulated directly by T3. Maximum binding capacities for myocardial Ca2+ channels and beta-receptors were determined by binding studies with [3H]PN200-110 and [125I]iodocyanopindolol in short-term and long-term hyper- and hypothyroid rats. After 2 and 8 weeks, Ca(2+)-channel maximum binding capacities were reduced by 25% and 23% in hyperthyroid rats (p < 0.05) and increased by 33% and 23% in hypothyroid rats (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)