Triggers and mediators of acute exercise-induced cardioprotection
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Introduction: Acute exercise, consisting of 1 to 3 bouts of 60 to 100 minutes, is capable of preconditioning the myocardium against ischemia-reperfusion (I/R) injury. We previously reported that elevated heat shock protein 70 (HSP70) is not required for this cardioprotective effect. The agent or agents that trigger and mediate this preconditioning effect are still not understood, but may involve the production of reactive oxygen species (ROS) during exercise as a trigger, and the production of nitric oxide (NO) by nitric oxide synthase (NOS) during I/R or uncoupling of mitochondrial respiration as mediators. The purpose of the present studies was to determine the role of these potential triggers and mediators in acute exercise-induced (AEI) cardioprotection. Methods: Rats were randomly assigned to seven treatment groups: sedentary (SED); two days of treadmill exercise at 20 m/min, 6-degree grade, for 60 minutes (RUN); sedentary and injected with 100 mg/kg N-(2-Mercaptopropionyl)glycine (MPG, a potent ROS scavenger) (SED/MPG); exercise and injected with MPG (RUN/MPG); sedentary then perfused with 100 µM Lω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, a competitive inhibitor of NOS) (SED/L-N); exercise then perfused with LNAME (RUN/L-N); exercise in a 4°C environment (to prevent HSP70 increase) then perfused with L-NAME (CRUN/L-N). Twenty-four hours following the second exercise bout, or MPG injection, isolated-perfused working hearts were subjected to 22.5 minutes of global ischemia followed by 30 minutes of normoxic reperfusion. Portions of left ventricle were analyzed for several putative mediators of exerciseinduced cardioprotection including: HSP70, inducible (iNOS) or endothelial (eNOS) NOS, manganese superoxide dismutase (MnSOD), and catalase. Results: All exercise groups displayed improved recovery of cardiac function vs. sedentary groups, which was not inhibited by MPG injection or L-NAME perfusion. Also, all exercise groups had improved efficiency post-ischemia, suggesting that uncoupling does not mediate AEI cardioprotection. The only increases in protein expression were: HSP70 in RUN, RUN/MPG, and RUN/L-N; eNOS in CRUN/L-N; and catalase in SED/MPG and RUN/MPG. Conclusions: AEI cardioprotection appears to not be triggered by ROS production, is mediated by changes independent of eNOS or catalase expression and uncoupling, and can occur in the absence of increases in HSP70, MnSOD, and iNOS.