Abstract 222: Mechanism of the Late Phase of Exercise-Induced Preconditioning against Myocardial Infarction
We assessed whether short-term, mild exercise induces a late preconditioning (PC) effects against myocardial infarction (MI) and, if so, whether nitric oxide (NO) and protein kinase C ϵ (PKCϵ) play a role. After four days of acclimation, mice were subjected to 2 bouts/day of treadmill exercise (60 min at 15 m/min) for 2 consecutive days. At 24 h after the last bout of exercise, mice were subjected to a 30-min coronary artery occlusion followed by 24 h reperfusion. In the exercise group (group III, wild-type [WT] mice, n=11), infarct size (25.5 ± 2.1% of the region at risk) was significantly (P<0.05) reduced compared with the control groups (sham exercise, group II [63.4 ± 2.6%, n=9] and acute MI, group I [58.6 ± 1.8%, n=15]). This effect was abolished by pretreatment with the NOS inhibitor L-nitroarginine (L-NA, group V, 59.1 ± 2.8%, n=7) and the PKC inhibitor chelerythrine (CHE, group VII, 60.9 ± 3.7%, n=5). Moreover, the late PC effect of exercise was completely abrogated in endothelial NO synthase knockout (eNOS −/−) mice (group X, 61.0 ± 3.9%, n=8). Compared with sham-exercised hearts, phosphorylated eNOS at Ser-1177 and nitrite/nitrate levels were elevated at 30 min after the last bout of exercise. PKCϵ activity and PKCϵ translocation were significantly and selectively increased at 30 min after exercise in WT mice but not in eNOS −/− mice. We conclude that 1) even short, mild exercise induces a delayed PC effect that affords protection against MI; 2) this cardioprotective effect is dependent on activation of eNOS, on eNOS-derived NO generation, and on PKCϵ activation; 3) the activation of PKCϵ is dependent on (and hence downstream of) eNOS. Thus, eNOS is the trigger of PC induced by mild exercise.