Increase in oxygen uptake due to arachidonic acid is oxygen dependent in the perfused liver
Nakagawa, Y.; Matsumura, T.; Goto, M.; Qu, W.; Kauffman, F.C.; Thurman, R.G.
American Journal of Physiology 266(5 Pt 1): G953-G959
ISSN/ISBN: 0002-9513 PMID: 8203541 Accession: 008847302
The purpose of this study was to determine whether the effect of arachidonic 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 cntdot g-1 cntdot h-1. When the flow rate was doubled to make the hepatic O-2 gradient shallower, the increase in O-2 uptake due to arachidonate was two to three times larger (i.e., apprx 50 pmol cntdot g-1 cntdot h-1). In livers perfused in the retrograde direction, maximal rates 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 regions. 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 not in isolated hepatocytes. In addition, conditioned medium from Kupffer cells incubated at high O-2 tension stimulated parenchymal cell O-2 uptake. Furthermore, arachidonate increased intracellular Ca-2+ in isolated Kupffer cells in a dose-dependent manner. These findings suggest that eicosanoids produced by nonparenchymal cells participate in a hepatic O-2 sensor mechanism involving Ca-2+ that regulates O-2 uptake by parenchymal cells in the liver.