Left ventricular phosphorylation patterns of Akt and ERK1/2 after triiodothyronine intracoronary perfusion in isolated hearts and short-term treatment in Wistar rats.

OBJECTIVES

To determine the effects of triiodothyronine (T3) intracoronary perfusion in isolated hearts and short-term administration in rats on the left ventricular (LV) phosphorylation patterns of Akt and ERK1/2.

MATERIALS AND METHODS

Cardiodynamic and hemodynamic parameters were evaluated in Langendorff-perfused hearts. Left ventricles were used for histomorphometric and Western blot analyses. Short-term hyperthyroidism was established by T3 (500 μg.kg.d; subcutaneous injection) for 1 (T3), 3 (T3), and 10 (T3) days.

RESULTS

Isolated hearts receiving T3 perfusion did not modify LV developed pressure, +dP/dt, -dP/dt, heart rate, and coronary perfusion pressure compared with vehicle-perfused hearts. P-ERK1/2 and p-Akt levels in LV tissues after 5, 15, or 60 min of T3 or vehicle perfusion were similar. Compared with their time-matched controls, isolated hearts of T3 and T3 rats exhibited LV hypertrophy and increased absolute values of +dP/dt and -dP/dt (i.e., positive inotropic and lusitropic effects). P-ERK1/2 decreased in LV tissues of T3 and T3 but not in those of T3 rats, and p-Akt levels augmented in left ventricles of T3 and stayed unaltered in those of T3 and T3 rats.

CONCLUSION

T3 intracoronary perfusion did not alter cardiodynamics and hemodynamics nor influence the activation of Akt and ERK of normal hearts. Accordingly, the rapid non-genomic effects of T3 were not evident. Short-term T3 treatment provoked cardiac hypertrophy coincidental with increased LV function and associated with transient Akt activation and cyclic ERK1/2 inhibition; which implies activation of physiological hypertrophy signaling and deactivation of pathological hypertrophy signaling, respectively.