ENDOTOXIN TRIGGERS THE EXPRESSION OF AN INDUCIBLE ISOFORM OF NITRIC-OXIDE SYNTHASE AND THE FORMATION OF PEROXYNITRITE IN THE RAT AORTA IN-VIVO

The free radicals nitric oxide (. NO) and superoxide (O-2(-)) are known to react to form peroxynitrite (ONOO-), a highly reactive species, Peroxynitrite has been suggested to play an important role in the cellular damage associated with the overproduction of . NO, but there are very limited data regarding its in vivo formation. Were we demonstrate that injection of endotoxin into rats leads to the expression of an inducible isoform of . NO synthase (iNOS) in the thoracic aorta at 6 h and an increase in the circulating levels of nitrite/nitrate. Moreover, at the same time point, there is a marked increase in the immunoreactivity of nitrotyrosine, a marker of peroxynitrite in the aorta, The formation of nitrotyrosine was prevented by inhibiting the activity of NOS by N-G-methyl-L-arginine in vivo, Our data suggest that during endotoxin shock, part of . NO, produced following the induction of iNOS, is converted into peroxynitrite in the vicinity of large blood vessels, The demonstration of the in vivo formation of peroxynitrite at sites of . NO overproduction may necessitate the development of novel and additional approaches for limiting or preventing . NO-related cytotoxic or vasodilatory actions during circulatory shock.