Nature Medicine
1, 804 - 809 (1995)
doi:10.1038/nm0895-804
Enzyme-independent formation of nitric oxide in biological tissuesJay L. Zweier1, 2, Penghai Wang1, Alexandre Samouilov1
& Periannan Kuppusamy1
1Molecular and Cellular Biophysics Laboratories, Department of Medicine, Division of Cardiology, and the Electron Paramagnetic Resonance Center, The Johns Hopkins Medical Institutions, Johns Hopkins Bayview Medical Center, 5501 Hopkins Bayview Circle, Baltimore, Maryland 21224, USA
2Correspondence should be addressed to J.L.Z. at the EPR Center. The gaseous free radical nitric oxide (NO ) is an important regulator of a variety of biological functions and also has a role in the pathogenesis of cellular injury. It has been generally accepted that NO is solely generated in biological tissues by specific nitric oxide synthases, NOSs, which metabolize arginine to citrulline with the formation of NO. We report that NO can also be generated in the ischaemic heart by direct reduction of nitrite to NO under the acidotic and highly reduced conditions that occur. This NO formation is not blocked by NOS inhibitors, and with long periods of ischaemia progressing to necrosis, this mechanism of NO formation predominates. We observe that enzyme-independent NO generation results in myocardial injury with a loss of contractile function. The existence of this enzyme independent mechanism of NO formation has important implications in our understanding of the pathogenesis and treatment of tissue injury.
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