Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning

Authors

  • Péter Ferdinandy,

    Corresponding author
    1. Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720 Hungary
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  • Richard Schulz

    1. Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada
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Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720 Hungary. E-mail: PETER@BIOCH.SZOTE.U-SZEGED.hu

Abstract

There appears to be a controversy in the study of myocardial ischaemia-reperfusion injury and preconditioning whether nitric oxide (NO) plays a protective or detrimental role. A number of findings and the interpretation of the results to date do not support such a controversy. An understanding of the latest developments in NO, superoxide (O2·) and peroxynitrite (ONOO) biology, as well as the various ischaemic animal models utilized is necessary to resolve the apparent controversy. NO is an important cardioprotective molecule via its vasodilator, antioxidant, antiplatelet, and antineutrophil actions and it is essential for normal heart function. However, NO is detrimental if it combines with O2· to form ONOO which rapidly decomposes to highly reactive oxidant species. There is a critical balance between cellular concentrations of NO, O2·, and superoxide dismutase which physiologically favour NO production but in pathological conditions such as ischaemia and reperfusion result in ONOO formation. In contrast, exposure of the heart to brief episode(s) of ischaemia markedly enhances its ability to withstand a subsequent ischaemic injury. The triggering of this endogenous cardioprotective mechanism known as preconditioning requires both NO and O2· synthesis. However, preconditioning in turn attenuates the overproduction of NO, O2· and ONOO during a subsequent episode of ischaemia and reperfusion, thereby protecting the heart. Here we review the roles of NO, O2·, and ONOO in both ischaemia-reperfusion injury and preconditioning.

British Journal of Pharmacology (2003) 138, 532–543. doi:10.1038/sj.bjp.0705080

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