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 delayed action at the level of the nucleus and acute effects on the plasma membrane. Here we present evidence for a direct and rapid stimulatory effect of TH in the intact normal heart. In the isolated perfused rat heart, 3,5,3'-tri-iodothyronine (T3) 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 T3 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 as 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-T3 > L-thyroxine (T4) = D-T3 > D-T4; 3,3',5'-tri-iodothyronine (rT3), 3,5,-L-di-iodothyronine and DL-thyronine had no effect). The calcium blockers nifedipine and verapamil, at concentrations of 10(-8) - 10(-5) M given before or after the addition of T3 (10(-9) - 10(-6) M), inhibited the T3-induced increase in cardiac inotropic activity in a time- and dose-related fashion. We suggest that the acute effect of TH in the heart is plasma membrane-mediated and calcium-dependent.
Segal
J
J
Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah University Hospital, Jerusalem, Israel.
Masalha
S
S
Schwalb
H
H
Merin
G
G
Borman
J B
JB
Uretzky
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013974:Thyroxine / Q000494:pharmacology; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D014284:Triiodothyronine; D014700:Verapamil; D009543:Nifedipine; D013974:Thyroxine