Summary
The endothelium derived relaxing factor (EDRF), that was recognized to have vasodilatatory effects in vascular smooth muscle, prevents platelet aggregation and adhesion of platelets as well as polymorphonuclear leukocytes to endothelium. EDRF is most likely synonymous with nitric oxide (NO). This simple chemical compound exerts most of its vital physiological functions by stimulation of guanylate-cyclase. NO was also found to play a significant role in various physiological functions and pathophysiological disorders. The basis for these activities may be the deleterious decrease of the various physiological functions by rapid decomposition of NO, especially in the presence of superoxide radicals (O\(\left( {O_2^{\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\cdot}$}}{ - } }} \right)\). In O\({O_2}^{\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\cdot}$}}{ - } }\) generating tissues, NO rapidly converts to peroxynitrite (ONOO¯), a compound with properties similar to hydroxyl radicals. Macrophages generating both NO and O\({O_2}^{\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\cdot}$}}{ - } }\) during their activities in inflammation were proposed to contribute to tissue injury via the formation of ONOO¯. Endothelium cells appear also capable of generating NO and O\({O_2}^{\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\cdot}$}}{ - } }\) radicals simultaneously. The subsequent formation of an ON00 may cause oxidative degradation of low density lipoproteins. The protection of the oxidant-induced damage by hydroxyl radical scavengers revealed also the possibility of OH, formation via homolitic cleavage of ONOO¯. It is becoming more clear that SOD exerts important functions in oxidant/antioxidant homeostasis of the tissue. SOD not only prevents conversion of NO to ONOO¯ by removing O\({O_2}^{\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\cdot}$}}{ - } }\) from the reaction, it also seems to be involved in converting NO¯ from an intermediate form of EDRF to NO. These functions appear to be important in the control of ischemia/reperfusion damage as demonstrated by the protecting effect of SOD in gastric mucosa alterations. On the other hand raising tissue levels of NO above normal (which was shown to occur following application of butylated hydroxytoluene) may cause increased gene expression (including oncogenes) via disturbance of cellular c-GMP levels. Another example of the genotoxic effect of exogenous nitrocompounds is the DNA-damaging activity of a biotransformation product of 2-nitropropane.
The present chapter reports on the existence and tissue regulation of NO and NO-related compounds and their involvement in various physiological disorders.
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© 1993 Birkhäuser Verlag
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Nohl, H. (1993). Nitric Oxide and Related Radicals. In: Poli, G., Albano, E., Dianzani, M.U. (eds) Free Radicals: from Basic Science to Medicine. Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9116-5_4
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DOI: https://doi.org/10.1007/978-3-0348-9116-5_4
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