Respiration Physiology (1987) 70, 131-14l 131 Elsevier RSP 01338 Effect of Po2 on prostaglandin E 2 production in renal cell cultures S. Roszinski and W. Jelkmann Physiologisches Institut. Medizinische UniversiRit zu Liibeck, D-2400 Liibeck, F.R.G. (Accepted for publication 6 June 1987) Abstract. There is evidence both from/n 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 PGEz/mg protein at 7 mm Hg 02, compared to 52 ng/mg at 143 mm Hg 02, but was lowered to 26 ng/mg at 3 mm Hg 02. PGE 2 production by the pig kidney tubule cell lines LLC-PK 1 and PK-15 was insensitive to Po2 changes. Because PGE 2 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 Po: 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. Hypoxia; Kidney; Mesangial cells; Prostaglandin E2 The synthesis of prostanoids in various tissues is stimulated by hypoxic conditions such as low arterial Po2 or ischemia (cf Markelonis and Garbus, 1975). For example, the production of prostacyclin increases when isolated hearts (Kirstein, 1979; Wennmalm, 1979) or kidneys (Burdowski et aL, 1980) are perfused with hypoxic solutions. Studies on isolated arteries indicate that the vasodilatory response to hypoxia is mediated, at least partially, by the release of prostaglandin E (Kalsner, 1977) and of prostacyclin (Busse et aL, 1984). On the other hand, lowered prostanoid synthesis could be involved in the closure of the ductus arteriosus when the arterial Po2 increases after birth (Coceani et aL, 1976). In addition to their effects on blood flow, prostaglandin E2 and prostacyclin are thought to improve the 0 2 supply to tissues by stimulating erythropoiesis (cf Fisher, Correspondence address: Wolfgang Jelkmann, M.D., Physiologisches Institut, Medizinische Universit~it zu Lfibeck, D-2400 Libeck, F.R.G. 0034-5687/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)