Effect of exercise preconditioning on myocardial content of Sphingosine1-phosphate and its mechanism in rats after exhaustive exercise

OBJECTIVE: This study aimed to investigate the effects of exercise preconditioning on rat myocardial Sphingosine1-phosphate(S1P) content and its potential mechanisms of heart protection. METHODS: A rat model of exercise preconditioning followed by exhaustive exercise was established. Rats were randomized to four groups: control (C), exercise preconditioning (EP), EP plus the S1PR1-selective antagonist W146 (EP + W146), and EP plus the MEK1/2 inhibitor PD98059 (EP + PD98059). Following a final exhaustive swim, comparisons across groups revealed that EP attenuated myocardial injury and apoptosis, an effect which was abolished by both W146 and PD98059. RESULTS: 1. Exercise preconditioning (EP) significantly attenuated exhaustive exercise-induced myocardial injury and apoptosis (P < 0.001); 2. EP significantly elevated myocardial S1P levels (P = 0.002), and S1PR1-selective antagonist (W146) abolished this cardioprotective effect (P = 0.016 for apoptosis); 3. Most importantly, MAPK pathway inhibition (PD98059) abrogated the protective effect of EP, as evidenced by significantly increased apoptosis (P = 0.002), despite unaltered S1P levels. CONCLUSION: In summary, beyond confirming S1P elevation with exercise preconditioning, our findings propose the S1P→MAPK signaling axis as a novel mechanistic pathway warranting future validation.