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.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002752:Chlorthalidone / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex / Q000201:enzymology*; D010646:Phentolamine / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013843:Thiazines / Q000494:pharmacology
D004232:Diuretics; D011458:Prostaglandins E; D013843:Thiazines; D006830:Hydralazine; D005665:Furosemide; D000429:Alcohol Oxidoreductases; D006911:Hydroxyprostaglandin Dehydrogenases; D004976:Ethacrynic Acid; D002752:Chlorthalidone; D007213:Indomethacin; D010646:Phentolamine