Inhibition of renal PGE2-9-ketoreductase by diuretics

The metabolism of PGE2 by extracts of renal cortex is species dependent. In the rat PGE2-15-hydroxydehydrogenase initiates metabolism whereas in the rabbit PGE2-9-ketoreductase predominates. In man both mechanisms may operate. Each of the metabolic enzymes, which limits the vasodilator-diuretic actions of PGE2, was inhibited by ethacrynic acid, furosemide and indomethacin. Some inhibition of PGE2-9-ketoreductase was also observed with chlorthalidone, hydralazine and phentolamine but the thiazide diuretics and a number of other cardiovascular-active agents were without significant effect. We conclude that the inhibition of PGE2-9-ketoreductase and PGE2-15-hydroxydehydrogeanse could contribute to the mechanism of action of the non-thiaxide diuretics in man.