Another potential mechanism by which oxidant stress may damage tissue is by formation of toxic peroxynitrite. This is highly controversial, given the abundance of intracytoplasmic SOD.2 Oyama et al.55 demonstrated that cytokine induction of NOS2 is associated with evidence of nitrotyrosine formation, a marker of ONOO- production, in canine myocardium. In the setting of cytokine exposure, induction of superoxide-generating systems (eg, xanthine oxidase) has been demonstrated, enhancing the likelihood of peroxynitrite formation.56 We demonstrated a 4-fold increase in xanthine oxidase concentration in dogs with pacing-induced dilated cardiomyopathy and an improvement in myocardial mechano-energetic efficiency in response to xanthine oxidase inhibition with allopurinol.57 We demonstrated cross talk between NOS and xanthine oxidase signaling in the regulation of myocardial energetics (unpublished observations). Whether peroxynitrite formation contributes to these effects remains to be determined.
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