ABSTRACT

The apparent toxicity of nitric oxide observed in biological systems is controversial (Lipton et al., 1993). Many believe that nitric oxide itself possesses little toxicity but instead is a precursor to a fairly potent oxidant called peroxynitrite (Beckman et al., 1990). Peroxynitrite can be formed in a test tube by mixing superoxide and nitric oxide (Bough and Zafiriou, 1985). The rate of this reaction is 6.7×109 M−1 s−1 (Thomson et al., 1995) which is even faster than the enzymatic rate between superoxide and superoxide dismustase (SOD) (Riley et al., 1991). This is an extremely fast reaction and is in fact close to the diffusion limited rate (1010 M-1 s-1) (Visscher et al., 1988). This means that when superoxide and nitric oxide collide there is basically no other option but to reactively condense and form peroxynitrite. In vivo, there is ample opportunity for superoxide and nitric oxide to collide. The isoenzymatic systems of nitric oxide sythase in all of its forms and the inflammatory cell systems as well as mitochondrial electron leakages are ubiquitous sources for nitric oxide and superoxide respectively. As such, these sources virtually guarantee that peroxynitrite will be formed especially during critical events of pathophysiology.