PEROXYNITRITE-MEDIATED OXIDATION OF DIHYDRORHODAMINE-123 OCCURS IN EARLY STAGES OF ENDOTOXIC AND HEMORRHAGIC-SHOCK AND ISCHEMIA-REPERFUSION INJURY

To quantify peroxynitrite production during shock, we measured oxidation of dihydrorhodamine 123 in rats. In endotoxic and hemorrhagic shock and splanchic ischemia-reperfusion, dihydrorhodamine oxidation rapidly increased, which was prevented by inhibition of endothelial nitric oxide (. NO) synthase (ecNOS). Thus, peroxynitrite is already formed at early stages of shock from ecNOS-derived . NO. Overproduction of . NO by the inducible NOS at late shock was not associated with additional increases in dihydrorhodamine oxidation, ecNOS inhibition enhanced dihydrorhodamine oxidation in control rats. These latter findings may be explained by . NO-mediated inhibition of peroxynitrite-induced dihydrorhodamine oxidation, a phenomenon also observed in vitro.