Figure 5. Inhibition of p38 MAPK restores depressed contractility in Dusp1/4^−/− mice and isolated cardiomyocytes.

A and B, Invasive hemodynamic assessment of contraction (Max dP/dt) and relaxation (Min dP/dt) velocities in anesthetized, close-chested Wt and Dusp1/4^−/− (DKO) mice fed for 2 weeks with either control chow (Con.-chow) or p38 inhibitor SB731445-formulated chow (50 mg/kg/day; SB-chow). (N=5 or more mice per group) (*p<0.01 vs. Wt Con.-chow; #p<0.01 vs. DKO Con.-chow). C, Representative traces of fura-2 F₃₄₀/F₃₈₀ fluorescence ratio (black trace) and myocytes shortening (red trace) recordings from Wt or Dusp1/4^−/− (DKO) isolated adult cardiomyocytes in the absence or presence of p38 inhibitor SB239063 (50 μM; SB). D–G, Average maximal peak amplitude of electrically evoked Ca²⁺ transients, time constant of Ca²⁺ decay, average maximal Ca²⁺ response to a 10 mM caffeine bolus, and percentage of shortening in isolated adult cardiomyocytes from the indicated genotypes in absence (Control) or presence of p38 inhibitor SB239063 (50 μM; SB). At least 4 animals were used, and the total number of cells analyzed is indicated in the bars (*p<0.05 vs. Wt Control; #p<0.05 vs. DKO Control).