The Inotropic Effect of the Active Metabolite of Levosimendan, OR-1896, Is Mediated through Inhibition of PDE3 in Rat Ventricular Myocardium
Fig 1
The inotropic response to OR-1896 is enhanced by PDE4 inhibition and absent in the presence of PDE3 inhibition.
The figure shows representative original tracings of experiments showing the effect of increasing concentrations of OR-1896 (OR) alone and in the presence of PDE4 (A) and PDE3 (B) inhibitors. A) Effect of OR-1896 in increasing concentrations (OR-7: 100 nM, OR-6: 1 μM and OR-5: 10 μM, n = 6) and the effect of OR-1896 in the presence of the PDE4 inhibitor rolipram (Rol, 10 μM, n = 6). B) Effect of OR-1896 in the presence of a PDE3 inhibitor, either cilostamide (Cil, 1 μM, n = 6) or milrinone (Mil, 1 μM). A, B) EMD57033 (EMD, 3 μM) was added after OR-5. Isoprenaline (Iso, 100 μM) administered at the end gave the maximum inotropic response achievable in the strip. C) Bar graph showing the inotropic response to different concentrations of OR-1896 in the presence and absence (Ctr) of PDE inhibitors in rat myocardial strips (n = 6). D) Bar graph comparing the inotropic response of OR-1896 (1 μM) to the inotropic response of different PDE inhibitors in rat ventricular strips (n = 6). All experiments were conducted on rat ventricular muscle strips in the absence of timolol and in the presence of α1-AR (prazosin, 100 nM) and muscarinic receptor blockade (atropine, 1 μM). Basal force values for each group (mN): OR-1896: 4.3±0.7; Rol: 3.5±0.5; Cil: 3.2±0.5; Mil: 2.6±0.3.