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

OBJECTIVE(S): 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(-1).d(-1); subcutaneous injection) for 1 (T3(1d)), 3 (T3(3d)), and 10 (T3(10d)) days. RESULTS: Isolated hearts receiving T3 perfusion did not modify LV developed pressure, +dP/dt(max), -dP/dt(min), 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(3d) and T3(10d) rats exhibited LV hypertrophy and increased absolute values of +dP/dt(max) and -dP/dt(min) (i.e., positive inotropic and lusitropic effects). P-ERK1/2 decreased in LV tissues of T3(1d) and T3(10d) but not in those of T3(3d) rats, and p-Akt levels augmented in left ventricles of T3(3d) and stayed unaltered in those of T3(1d) and T3(10d) 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.