STIMULATION OF OXYGEN-UPTAKE BY PROSTAGLANDIN E-2 IS OXYGEN-DEPENDENTIN PERFUSED-RAT-LIVER

The aim of this study was to determine if the effect of prostaglandin E-2 (PGE(2)) on hepatic oxygen uptake was affected by oxygen tension. Livers from fed female Sprague-Dawley rats were perfused at normal or high flow rates (4 or 8 ml g-l min-l) to vary local oxygen tension wit hin the liver lobule. During perfusion at normal flow rates, PGE(2) (5 mu M) infusion increased oxygen uptake by about 50 mu mol.g(-1).h(-1) ; however, when livers were perfused at high flow rates, the increase was nearly twice as large. Simultaneously, glucose output was increase d rapidly by about 50%, whereas glycolysis was decreased about 60%. Wh en flow rate was held constant, increases in oxygen uptake due to PGE( 2) were proportional to oxygen delivery. Infusion of PGE(2) into liver s perfused at normal flow rates increased state 3 rates of oxygen upta ke of subsequently isolated mitochondria by about 25%; however, rates were increased 50-75% in mitochondria isolated from livers perfused at high flow rates. Thus it is concluded that PGE(2) stimulates oxygen u ptake via mechanisms regulated by oxygen tension in perfused rat liver . High flow rates also increased basal rates of oxygen uptake: this in crease was prevented by inactivation of Kupffer cells with GdCl3. In a ddition, conditioned medium from Kupffer cells incubated at high oxyge n tension (75% oxygen) stimulated oxygen uptake of isolated parenchyma l cells by >30% and elevated PGE2 production about twofold compared wi th Kupffer cells exposed to normal air-saturated buffer (21% oxygen). These effects were blocked completely by both indomethacin and nisoldi pine. These data support the hypothesis that oxygen stimulates Kupffer cells to release mediators such as PGE(2) which elevate oxygen consum ption in parenchymal cells, possibly by mechanisms involving cyclooxyg enase and calcium channels.