Regulation of β‐AR cytoplasmic cAMP signals by PDE3 and PDE4 in LVMs and RVMs. A, left, average time course of cAMP levels measured in the cytoplasm with Epac2‐camps following β‐AR stimulation with Iso (100 nmol/L, 15 seconds) alone (gray and black lines, data from Figure 3B) or during administration of the PDE3 inhibitor cilostamide (Cil, 1 μmol/L, white circles: LVMs, n=13 from 3 dogs; black circles: RVMs, n=17 from 7 dogs). Right, Bar graphs representing the average maximal amplitude and time to 50% recovery (t1/2off) of the cytoplasmic cAMP transients induced by Iso alone or Iso with Cil in LVMs (n=13) and RVMs (n=17). B, left, average time course of cytosolic cAMP levels following β‐AR stimulation with Iso (100 nmol/L, 15 seconds) alone or during administration of the PDE4 inhibitor Ro 20‐1724 (Ro, 10 μmol/L; white circles: LVMs, n=21 from 6 dogs; black circles: RVMs, n=24 from 5 dogs). Right, bar graphs representing the average maximal amplitude and time to 50% recovery (t1/2off) of the cAMP transients induced by Iso alone or Iso with Ro in LVMs (n=21) and LVMs (n=24). PDE inhibitors were added to the Iso solution and in the washout solution. Symbols and bar graphs indicate the mean±SEM. Statistical difference between Iso alone and Iso+PDE inhibitor in LVMs and RVMs is indicated as *, P<0.05; ***, P<0.001. AR indicates adrenergic; cAMP, cyclic adenosine monophosphate; LV, left ventricle; LVM, left ventricular myocyte; PDE, phosphodiesterase; RV, right ventricle; RVM, right ventricle myocyte.