Abstract
Background
Hyperoxic exposure in vivo (> 95% oxygen) attenuates ischemia-reperfusion injury, but the signaling mechanisms of this cardioprotection are not fully determined. We studied a possible role of nitric oxide (NO) and mitogen activated protein kinases (MAPK) in hyperoxic protection.
Methods
Mice (n = 7–9 in each group) were kept in normoxic or hyperoxic environments for 15 min prior to harvesting the heart and Langendorff perfusion with global ischemia (45 min) and reperfusion (60 min). Endpoints were cardiac function and infarct size. Additional hearts were collected to evaluate MAPK phosphorylation (immunoblot). The nitric oxide synthase inhibitor L-NAME, the ERK1/2 inhibitor PD98059 and the p38 MAPK inhibitor FR167653 were injected intraperitoneally before hyperoxia or normoxia.
Results
Hyperoxia improved postischemic functional recovery and reduced infarct size (p < 0.05). Hyperoxic exposure caused cardiac phosphorylation of the MAPK family members p38 and ERK1/2, but not JNK. L-NAME, PD98059 and FR167653 all reduced the protection afforded by hyperoxic exposure, but did not influence performance or infarction in hearts of normoxic mice. The hyperoxia-induced phosphorylation of ERK1/2 and p38 was reduced by L-NAME and both MAPK inhibitors.
Conclusion
Nitric oxide triggers hyperoxic protection, and ERK1/2 and p38 MAPK are involved in signaling of protection against ischemia-reperfusion injury.
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Ruusalepp, A., Czibik, G., Flatebø, T. et al. Myocardial protection evoked by hyperoxic exposure involves signaling through nitric oxide and mitogen activated protein kinases. Basic Res Cardiol 102, 318–326 (2007). https://doi.org/10.1007/s00395-007-0644-5
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DOI: https://doi.org/10.1007/s00395-007-0644-5