Effect of PO2 on prostaglandin E2 production in renal cell cultures

There is evidence both from in vivo and in vitro studies which suggests that hypoxia stimulates the synthesis of prostanoids in some tissues. In the present study, the in vitro production of prostaglandin E2 (PGE2) was studied in three different renal cell lines incubated at various PO2 values between 143 and 3 mm Hg for 24 h. In rat kidney mesangial cell cultures, PGE2 production increased up to 99 ng PGE2/mg protein at 7 mm Hg O2, compared to 52 ng/mg at 143 mm Hg O2, but was lowered at 26 ng/mg at 3 mm Hg O2. PGE2 production by the pig kidney tubule cell lines LLC-PK1 and PK-15 was insensitive to PO2 changes. Because PGE2 production is known to be Ca2+-dependent and was indeed stimulated by the Ca-ionophore A 23187, effects of hypoxia on 45Ca2+-fluxes were also studied. In none of the 3 cell lines, net 45Ca-influx was altered after incubation at low PO2. However, net 45Ca-efflux increased during hypoxic incubation of mesangial cells possibly as a result of intracellular Ca-mobilization. These results indicate that hypoxia stimulates PGE2 synthesis in mesangial but not in tubule cell cultures. However, at very low PO2 values, or anoxia, the formation of cyclic endoperoxides from arachidonic acid may be lowered. Since mesangiocytes are smooth muscle-like cells, the hypoxia-induced synthesis of relaxing prostanoids could play a role in the regulation of smooth muscle tone.