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 know n to react to form peroxynitrite (ONOO-), a highly reactive species, P eroxynitrite has been suggested to play an important role in the cellu lar damage associated with the overproduction of . NO, but there are v ery limited data regarding its in vivo formation. Were we demonstrate that injection of endotoxin into rats leads to the expression of an in ducible isoform of . NO synthase (iNOS) in the thoracic aorta at 6 h a nd an increase in the circulating levels of nitrite/nitrate. Moreover, at the same time point, there is a marked increase in the immunoreact ivity of nitrotyrosine, a marker of peroxynitrite in the aorta, The fo rmation of nitrotyrosine was prevented by inhibiting the activity of N OS by N-G-methyl-L-arginine in vivo, Our data suggest that during endo toxin shock, part of . NO, produced following the induction of iNOS, i s 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 ad ditional approaches for limiting or preventing . NO-related cytotoxic or vasodilatory actions during circulatory shock.