Abstract: | 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
. 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-PGF1α 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 16-keto- PGF1α levels, sulindac also significantly (p < 0.05) attenuated the elevated renal venous plasma 6-keto-PGF1α levels, compared to the vehicle group. Using lower doses, sulindac failed to reduce the endotoxin associate increased in either aortic or renal venous plasma 16-keto-PGF1α levels. Thus, sulindac failed to demonstrate any selective sparing effect on renal prostacyclin generation during endotoxemia. |