INCREASE IN OXYGEN-UPTAKE DUE TO ARACHIDONIC-ACID IS OXYGEN-DEPENDENTIN THE PERFUSED LIVER

The purpose of this study was to determine whether the effect of arach idonic acid on hepatic O-2 uptake is O-2 dependent and which region of the liver lobule it affects. In livers perfused at normal flow rates, infusion of arachidonate increased O-2 uptake significantly by about 20-25 mu mol.g(-1).h(-1). When the flow rate was doubled to make the h epatic O-2 gradient shallower, the increase in O-2 uptake due to arach idonate was two to three times larger (i.e., similar to 50 mu mol.g(-1 ).h(-1)). In livers perfused in the retrograde direction, maximal rate s of O-2 uptake were about twofold higher in upstream pericentral than in downstream periportal regions, and arachidonic acid nearly doubled O-2 uptake in downstream areas without affecting rates in upstream re gions. Thus it is concluded that arachidonate stimulates O-2 uptake in an O-2-dependent manner. This effect was sensitive to an inhibitor of the lipoxygenase, nordihydroguaiaretic acid, in perfused liver but no t in isolated hepatocytes. In addition, conditioned medium from Kupffe r cells incubated at high O-2 tension stimulated parenchymal cell. O-2 uptake. Furthermore, arachidonate increased intracellular Ca2+ in iso lated Kupffer cells in a dose-dependent manner. These findings suggest that eicosanoids produced by nonparenchymal cells participate in a he patic O-2 sensor mechanism involving Ca2+ that regulates O-2 uptake by parenchymal cells in the liver.