Possible modulation of rat renal prostaglandin production by oxygen

1 Geriatric Research, Education and Clinical Center, Veterans Administration Hospital, and Department of Medicine and Biochemistry, St. Louis University, St. Louis, Missouri 63125 The effect of oxygen on in vitro prostaglandin production by slices of rat renal inner medulla was evaluated. Oxygen increased prostaglandin production in a dose-response fashion. Double reciprocal plots of the relationship revealed a half-maximal stimulation of prostaglandin (PG) E 2 production by 15.1% or 143 µM O 2 and of PGF 2 by 16.8% or 160 µM O 2 . An increased prostaglandin production at 95% O 2 was measurable within 2 min of incubation and was maximal at approximately 15 min. Oxygen also increased inner medullary cyclic AMP content with a similar time course. Lowering oxygen did not alter the response of the inner medulla to increase cyclic AMP content when exposed to vasopressin. PGE 2 increased cyclic AMP at 5% O 2 but not at 95%, while PGF 2 was ineffective at either oxygen concentration. In the presence of structurally dissimilar prostaglandin synthetase inhibitors, indomethacin and sodium meclofenamate, there was a reduction of basal cyclic AMP content as well as prostaglandin production. PGE 2 increased cyclic AMP at 95% O 2 in the presence of prostaglandin synthetase inhibitors while PGF 2 remained inactive. This suggests that the oxygen-mediated increases in cyclic AMP content may be due to endogenously produced PGE 2 . The data are consistent with oxygen modulating inner medullary production of prostaglandins, and with endogenously produced prostaglandins exerting a hormone-like action in the inner medulla. Submitted on March 25, 1977