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Figure 2 Effect of tumor necrosis factor-alpha (TNF) (10 ng/ml) on mkk3^–/– (KO) and mkk3^+/+ (WT) hearts during coronary perfusion under conditions of constant flow. Data represented by mean ± SEM; n = 6 per group. (A) Left ventricular developed pressure (LVDP) before and during exposure to TNF. (B) Left ventricular volume versus LVDP measured after at least 15 min of TNF. (C) Perfusion pressure measured before and during TNF. (D) Upper part shows representative Western blots of total and phosphorylated p38-MAPK and HSP27 in hearts exposed to TNF for 15 min. Lower part depicts quantitative data expressed as fold increase relative to baseline (mean ± SEM; n = 3). TNF induces activation of p38-MAPK in mkk3^+/+ but not in mkk3^–/– hearts under constant flow conditions; however, this effect was less pronounced than under constant pressure (Fig. 1).