Peroxynitrite: Toxic or Protective in the Heart?

To the Editor: The literature is somewhat controversial as to whether peroxynitrite (ONOO–) is either cytotoxic or cytoprotective. An Editorial by Vinten-Johansen1 recently suggested that deleterious effects of ONOO– in the heart are predominantly observed in in vitro or ex vivo crystalloid buffer–perfused systems; however, ONOO– is cardioprotective if applied in vivo. Does the exogenous administration of ONOO– accurately reflect pathological conditions in which the endogenous generation of ONOO– within cells is enhanced?Because of the short half-life of ONOO– at physiological pH, it has very little chance to reach its cellular targets when it is applied via the blood, as it rapidly reacts with plasma proteins and thiols such as glutathione and cysteine. Thus, ONOO– is likely to be detoxified before it has a …