Endotoxemic shock is a systemic inflammatory response that is associated with increased nitric oxide (NO)
production by inducible NO synthase (iNOS) which contributes to hypotension, vascular hyporeactivity, and multiple
organ failure. Oxidative stress (OS) is a major contributing factor to high morbidity and mortality in endotoxemic shock.
We have previously demonstrated that endotoxin-induced fall in blood pressure is associated with an increase in nitrite
levels in serum, kidney, heart, thoracic aorta (TA), and superior mesenteric artery (SMA), a decrease in malondialdehyde
(MDA) levels in the kidney, heart, TA, and SMA, and an increase in myeloperoxidase (MPO) activity in the heart and
TA, but a decrease in the kidney and SMA of rats. In this study, we further investigated whether increased production of
iNOS-derived NO contributes to endotoxin induced changes in the biomarkers of OS in the liver, lungs, brain, spleen, and
femoral artery (FA) of rats. Endotoxin-induced increase in nitrite production was associated with a decrease in reduced
glutathione levels in the liver, lungs, brain, spleen, and FA. MPO activity was increased by endotoxin in the lungs, spleen,
and FA, but decreased in the liver and brain. MDA levels were increased by endotoxin in the lungs, brain, spleen, and FA,
but were decreased in the liver. Activities of superoxide dismutase and catalase were decreased in the liver and spleen, but
were increased in the lungs, brain, and FA. These effects of endotoxin were prevented by a selective iNOS inhibitor,
phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide. These data suggest that iNOS-derived NO mediates selective
organ-specific effects of endotoxin on OS.