Résumé
Exercise training is a preconditioning strategy to reduce heart ischemiareperfusion (IR) injuries. The activation of endothelial isoform of NOS (eNOS) by exercise is now recognized as playing a key part. However, eNOS is expressed in both coronary endothelial cells and cardiomyocytes, and which eNOS cellular compartment mediates the protective effects of exercise remains unknown. In this study we investigated the role of cardiomyocytes vs. endothelial eNOS in exercise cardioprotection. Rats (n=90) were assigned to sedentary (Sed) or exercised (Ex) group, and experiments were performed in isolated heart, cardiomyocytes or isolated left coronary artery (LCA). First, we observed that exercise increases eNOS activation (phosphorylation on Ser1177) and S-nitrosylation in whole heart but not at cardiomyocyte level. To investigate functional involvement of eNOS at myocyte level during IR cardioprotection, we exposed isolated cardiomyocytes to an anoxia-reoxygenation (AR) procedure in presence or not of L-NAME, an eNOS inhibitor. Exercise reduced cells death and improved cells contractility after AR, but no effect of L-NAME was observed, suggesting an eNOS-independent effect of exercise. Next, to evaluate the contribution of endothelial cells in exercise cardioprotection, an IR procedure was performed on Langendorff hearts, and LCA were isolated after reperfusion. The alteration of endothelium-dependent coronary relaxation induced by IR was mainly reduced in Ex group. To further explore the contribution of endothelium in this cardioprotection, we perfused hearts with Triton X-100 before IR to abolish coronary endothelial cells activity. This inactivation totally suppressed cardioprotective effects of exercise on both heart functional recovery after IR and infarct size, whereas no effect was observed in Sed group. Altogether, the results suggest that coronary endothelial cells rather than cardiomyocytes play a key role in the eNOSdependent cardioprotection of exercise.
The author hereby declares no conflict of interest