ACUTE EFFECT OF THYROID-HORMONE IN THE RAT-HEART - ROLE OF CALCIUM

Several observations provide some clues as to the possible mode of the regulatory action of thyroid hormone (TH) in the heart, indicating de layed action at the level of the nucleus and acute effects on the plas ma membrane. Here we present evidence for a direct and rapid stimulato ry effect of TH in the intact normal heart. In the isolated perfused r at heart, 3,5,3'-tri-iodothyronine (T-3) produced a positive inotropic effect increasing both the left ventricular peak systolic pressure (P ) and +dP/dt values, but had no significant effect on heart rate. This effect of T-3 was: (1) very rapid in onset (starting after 15 s) and transient, increasing gradually to reach a maximum (80% above control) at about 20 min, and declining progressively 20 to 30 min later; (2) dose-related and biphasic, occurring at physiological concentrations a s low as 1 pM (+dP/dt) and 10 pM (P), reaching a maximum at 1 nM, and decreasing at higher concentrations; and (3) thyroid hormone specific, as shown by the effects of several TH analogs (L-T-3>L-thyroxine (rT( 3))=D-T-3>D-T-4; 3,3',5'-tri-iodothyronine (rT(3)), 3,5,-L-di-iodothyr onine and DL-thyronine had no effect). The calcium blockers nifedipine and verapamil, at concentrations of 10(-8)-10(-5) M given before or a fter the addition of T-3 (10(-9)-10(-6) M), inhibited the T-3-induced increase in cardiac inotropic activity in a time-and dose-related fash ion. We suggest that the acute effect of TH in the heart is plasma mem brane-mediated and calcium-dependent.