Effect of P O 2 on prostaglandin E 2 production in renal cell cultures

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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 E 2 (PGE 2) was studied in three different renal cell lines incubated at various P O 2 values between 143 and 3 mm Hg for 24 h. In rat kidney mesangial cell cultures, PGE 2 production increased up to 99 ng PGE 2/mg protein at 7 mm Hg O 2, compared to 52 ng/mg at 143 mm Hg O 2, but was lowered to 26 ng/mg at 3 mm Hg O 2. PGE 2 production by the pig kidney tubule cell lines LLC-PK 1 and PK-15 was insensitive to P O 2 changes. Because PGE 2 production is known to be Ca 2+-dependent and was indeed stimulated by the Ca-ionophore A 23187, effects of hypoxia on 45Ca 2+-fluxes were also studied. In none of the 3 cell lines, net 45Ca-influx was altered after incubation at low P O 2 . 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 PGE 2 synthesis in mesangial but not in tubule cell cultures. However, at very low P O 2 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.