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.
Szabó
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Children's Hospital Medical Center, Division of Critical Care, Cincinnati, OH 45229, USA.
Salzman
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Ischiropoulos
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D000818:Animals; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D012235:Rhodamines / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*
D009566:Nitrates; D012235:Rhodamines; C058319:dihydrorhodamine 123; C039642:peroxynitric acid