REACTIVE OXYGEN INDUCING VASOCONSTRICTION IN THE ISOLATED-PERFUSED RAT-LIVER

The effect of reactive oxygen generation on intact livers was studied. Production of reactive oxygen species in perfused livers isolated fro m normal and endotoxin-treated rats was measured using chemically enha nced chemiluminescence. The resting state chemiluminescence of the liv ers increased on endotoxin administration and was maximal about 6 h af ter treatment. Chemiluminescence from the livers was further stimulate d severalfold by inclusion of phorbol myristate acetate in the perfusi on medium, reaching maximum intensity 3 h after endotoxin treatment. O xygen consumption by the endotoxin-treated liver showed a transient in crease followed by a significant decrease on phorbol myristate acetate stimulation, which was inhibited by dexamethasone. These results are consistent with the occurrence of a respiratory burst followed by oxyg en-radical-species-induced vasoconstriction in the intact perfused liv er. The evaluation of reactive oxygen species by resident and accumula ted macropharges in the intact liver is made possible by these studies , and related effects on the liver could be conveniently and quantitat ively followed using this model.