The ERK1/2 Signaling Pathway Is Involved in Sulfur Dioxide Preconditioning-Induced Protection against Cardiac Dysfunction in Isolated Perfused Rat Heart Subjected to Myocardial Ischemia/Reperfusion

Ischemia/reperfusion injury (IRI) occurs frequently during reperfusion of ischemic myocardium, and preconditioning has been regarded as one of the best strategies to prevent myocardial injury during the ischemia/reperfusion process. Our previous studies indicated that a small dose of sulfur dioxide (SO₂) used as preconditioning exerts cardioprotection. However, the mechanisms underlying the cardioprotection remain unclear. The present study was designed to examine if the extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway mediated protection against cardiac dysfunction after SO₂ preconditioning in isolated rat hearts subjected to ischemia/reperfusion (I/R). Langendorff heart perfusion was performed in vitro, where 56 male Wistar rats were randomly divided into seven groups: control group, 5 μmol/L SO₂ group (S5), 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) + 5 μmol/L SO₂ (PD98059 + S5) group, PD98059 group, I/R group, 5 μmol/L SO₂ + I/R (S5 + I/R) group and PD98059 + 5 μmol/L SO₂ + I/R (PD98059 + S5 + I/R) group. Cardiac function and myocardial phosphorylated ERK1/2 protein were measured. We found that I/R in isolated rat heart resulted in cardiac dysfunction with a significant increase in phosphorylated ERK1/2 protein. SO₂ preconditioning markedly suppressed phosphorylated ERK1/2 protein and improved cardiac function in isolated rat heart with I/R (p < 0.05). However, pre-treatment with PD98059 could prevent the above effects of SO₂ preconditioning. In conclusion, SO₂ preconditioning protected against cardiac dysfunction in isolated rat heart subjected to I/R via suppression of the over-activation of the ERK1/2 signaling pathway.