The Inotropic Effect of the Active Metabolite of Levosimendan, OR-1896, Is Mediated through Inhibition of PDE3 in Rat Ventricular Myocardium
Fig 4
OR-1896 causes cAMP increase by PDE3 inhibition.
A, C, E) Experimental readouts of cAMP measured as the FRET signal from the RII_epac sensor in isolated cardiomyocytes. All cells were primed with a small concentration of isoprenaline (5 nM) prior to PDE inhibition. Forskolin (Fsk, 3 μM) was administered at the end as a measure of the maximum achievable FRET response, indicating that the sensors were not fully saturated during measurements. The readouts are normalized to the maximal response to Fsk. B) Bar graph showing the FRET response to OR-1896 (OR, 1 μM), followed by rolipram (Rol, 10 μM) and the attenuated response to cilostamide (Cil, 1 μM) following OR-1896 + Rol compared to Rol alone (n = 38 cells from 3 animals) The FRET responses are compared to a set of cells that did not receive OR-1896 (Ctr). D) Bar graph showing the FRET response to OR-1896 and the attenuated response to Cil after OR-1896 (n = 26 cells from 2 animals). F) Bar graph showing the FRET response to Cil and the attenuated response to OR-1896 after Cil (n = 24 cells from 2 animals). Data are mean ± SEM, * = p<0.05, ** = p<0.05 compared to OR-1896 (Fig. 4D), *** = p<0.05 compared to Cil (Fig. 4F), # = p<0.005.