Sulindac does not preserve renal prostacyclin synthesis during endotoxemia.
Previous reports have suggested that sulindac is a unique non-steroidal anti-inflammatory (NSAID) agent, because it does not inhibit renal prostaglandin synthesis in doses that inhibit platelet thromboxane B2 synthesis when tested ex vivo. NSAIDS are of potential therapeutic benefit in the treatment of septic or endotoxic shock. Therefore, this study was designed to investigate the proposed unique action of sulindac in experimental endotoxemia. In the current study, the effect of sulindac on aortic, portal and renal venous immunoreactive (i) 6-keto-PGF1 alpha levels, the stable metabolite of prostacyclin, was investigated during endotoxemia in the rat. In doses sufficient to reduce the elevation in aortic and portal venous plasma i6-keto-PGF1 alpha levels, sulindac also significantly (p less than 0.05) attenuated the elevated renal venous plasma 6-keto-PGF1 alpha levels, compared to the vehicle group. Using lower doses, sulindac failed to reduce the endotoxin associated increase in either aortic or renal venous plasma i6-keto- PGF1 alpha levels. Thus, sulindac failed to demonstrate any selective sparing effect on renal prostacyclin generation during endotoxemia.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000818:Animals; D011464:Epoprostenol / Q000096:biosynthesis*; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives / Q000494:pharmacology*
D007192:Indenes; D013467:Sulindac; D015121:6-Ketoprostaglandin F1 alpha; C025462:sulindac sulfide; D011464:Epoprostenol