Figure 1. PDE1i stimulates contraction at less Ca²⁺ rise than PDE3i in guinea pig.

A) Representative sarcomere shortening (upper) and Ca²⁺ transients (lower) from cardiomyocytes treated with a selective inhibitor to PDE1 (214; 1μM), PDE3 (cilostamide - Cil; 1μM), PDE4 (rolipram - Rol; 10μM), or isoproterenol (Iso; 1nM) each in 0.1% DMSO versus DMSO alone. B, C) Summary data pairing before and after drug (clear and shaded background, respectively); repeated measures 2-way ANOVA and Sidak’s multiple comparison test (MCT) within each drug (P values shown). D) Impact of PDE1 vs PDE3 inhibition in presence of 10nM Fsk versus Fsk alone. E, F) Group data showing change from baseline for this experiment using either 10 or 100 nM Fsk; Kruskal-Wallis test within each Fsk dose; Dunn’s MCT P-values shown. G) Change in sarcomere shortening in absence or presence of PKA inhibitor (Rp-8-CPT-cAMPS, 100μM) in same treatment groups shown in panels D-F. Ordinary 2-way ANOVA with Sidak’s MCT for effect of PDE inhibitor ±PKA inhibitor. Interaction of PDEi and PKA inhibitor effects were P=0.047 and P=0.0035 for Fsk+214 and Fsk+Cil, respectively.