Inducible Nitric Oxide Synthase in Cardiac Adaptation to Ischemia

  • Ján Slezák
  • Jan Styk
  • Olga Slezakova
  • Gerd Wallukat
  • Peter Karczewski
  • Wolfgang Schulze
  • Igor B. Buchwalow
Part of the Progress in Experimental Cardiology book series (PREC, volume 6)

Summary

Cardiac ischaemia/reperfusion is well known as a disease of the myocytes, it is now clear that reactive oxygen species and their intermediates in conjunction with increased nitric oxide (NO) production during and after ischemia determine the second window of protection. However, regulatory mechanisms of NO modulation during ischaemia/reperfusion are poorly understood. Assuming that increased expression of NO synthases (NOS) could be involved in mediation of cardioprotective effect of preconditioning, we preconditioned cultured neonatal rat cardiocytes with hypoxia, 10εM norepinephrine, or 1εM H2O2. Immunohistochemical assay of an inducible NOS isoform (NOS2) revealed that norepinephrine, hypoxia and H2O2 enhanced the expression of NOS2 in cardiomyocytes, both along contractile fibers and in a cytoplasmic granular component, apparently in mitochondria. Inhibition of NOS2 expression or NOS2 activity abolished the protective preconditioning effect of hypoxia treatment. Hence, NO is implicated as a trigger in this model of preconditioning via activation of inducible NOS isoform. These data provide evidence that an increased NO generation due to induction of inducible NOS, following ischaemia/reperfusion, might be associated with increased myocardial tolerance to infarction.

Key words

nitric oxide synthase myocardium ischemia reperfusion preconditioning cardiac adaptation 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Ján Slezák
    • 1
  • Jan Styk
    • 1
  • Olga Slezakova
    • 1
  • Gerd Wallukat
    • 2
  • Peter Karczewski
    • 2
  • Wolfgang Schulze
    • 2
  • Igor B. Buchwalow
    • 2
    • 3
  1. 1.Institute for Heart Research, Slovak Academy of Sciences; Faculty of MedicineCommenius UniversityBratislavaSlovak Republic
  2. 2.Max-Delbruck-Center for Molecular MedicineBerlinGermany
  3. 3.Department of Medicine B and Central Ultrastructure Research Team, IZKFUniversity of MünsterMünsterGermany

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