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Figure 4 Effect of 1 µmol/l SB203580 (SB) on tumor necrosis factor-alpha (TNF )-induced contractile dysfunction. Hearts from outbred C56BL/6 mice were perfused under constant pressure or constant flow conditions. SB was solubilized in dimethyl sulfoxide (DMSO). Hearts were exposed to TNF (10 ng/ml) for 15 min, SB (1 µmol/l), or DMSO (<0.01%) for 20 min. Data represent mean ± SEM; n = 6 per group. (A) Left ventricular developed pressure (LVDP) and (B) coronary flow with constant pressure perfusion. (C) LVDP and (D) perfusion pressure recorded under constant flow conditions. SB reduced TNF-induced contractile dysfunction with constant pressure and to a lesser extent with constant flow. Surprisingly, SB reversed TNF-induced coronary vasoconstriction. (E) Upper part shows representative Western blots of total and phosphorylated p38-MAPK and HSP27 in hearts exposed to TNF, SB, DMSO, and SB + TNF under constant pressure. Lower part depicts quantitative data expressed as phosphorylation increase related to total amount for a given protein (mean ± SEM; n = 3). NA = normalization not appropriate.
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