Ischemic postconditioning protects the heart against ischemia–reperfusion injury via neuronal nitric oxide synthase in the sarcoplasmic reticulum and mitochondria

As Ser852 in neuronal NOS is an inactive site, these results suggest that nNOS activation was partially suppressed at early reperfusion but that ischemic postconditioning restored nNOS activity in the cytosol

L Hu; J Wang; H Zhu; X Wu; L Zhou; Y Song; S Zhu; M Hao; C Liu; Y Fan; Y Wang; Q Li


Scholarcy highlights

  • Myocardial I/R injury is initiated within the first minutes of reperfusion, and this period represents a valuable 'window of opportunity' for myocardial protection. The most effective strategies are executed in the first minutes of reperfusion, such as ischemic postconditioning
  • Results neuronal NOS was involved in the cardioprotection of IPostC against I/R injury
  • NNOS inhibitors treatment alone during the reperfusion improved the contractile function of the hearts subjected to I/R because it improved the recovery of left ventricular developed pressure at the end of reperfusion
  • The primary finding in this study is that IPostC protected isolated mouse hearts against I/R injury partially via an nNOSmediated pathway
  • We demonstrated that the selective nNOS inhibitor L-VNIO abolished the cardioprotection of IPostC against I/R injury and unexpectedly decreased myocardial I/R injury to the same extent as IPostC when administered alone during reperfusion
  • Cardiac nitroso-redox imbalances are found in nNOS− / −24 and ob/ob mice because of decreased nNOS and increased reactive oxygen species production in the myocardium, which makes nNOS− / − mice more vulnerable to serious injury and mortality after I/R compared with WT mice
  • ischemic postconditioning decreased oxidative stress partially by regulating uncoupled neuronal NOS and the nNOS/AMPK/PGC-1α/superoxide dismutase axis and improved sarcoplasmic reticulum function by increasing SR Ca2+ load

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