IN-SITU MEASUREMENT OF NITRIC-OXIDE, SUPEROXIDE AND PEROXYNITRITE DURING ENDOTOXEMIA

We report in vivo and ex vivo measurements of nitric oxide (electroche mical), ex vivo in situ measurements of superoxide (chemiluminescence) and peroxynitrite (chemiluminescence) and delineate the effect of end otoxemia on nitric oxide, superoxide and peroxynitrite release in aort a of rats. Nitric oxide release was measured in the aorta wall. An inc rease of nitric oxide concentration was observed immediately after adm inistration of lipopolysaccharide (Escherichia coli serotype 0127: B8, 20 mg/kg), reaching a plateau (50 nmol/L) after 180+/-50 seconds; the plateau was followed by decreasing nitric oxide concentration and its subsequent gradual small increase after 45 minutes. Superoxide and pe roxynitrite production increased dramatically during endotoxemia. Supe roxide concentration increased from 10+/-2 nmol/L to 28+/-3 nmol/L at one hour, and reached a 50 nmol/L plateau at 4 hours. The pattern of p eroxynitrite release paralleled the pattern of superoxide release duri ng the time course of endotoxemia. Diametrical alteration of nitric ox ide and superoxide concentration with subsequent production of peroxyn itrite may be a major cause of endothelial cell injury during endotoxe mia.