Acute effects of the anti-inflammatory cyclooxygenase-2 selective inhibitor, flosulide, on renal plasma flow and glomerular filtration rate in rats.
Nephrotoxicity of nonsteroidal anti-inflammatory drugs is associated with other risk factors (volume-depletion) and may be secondary to functional changes mediated by the inhibition of renal cyclooxygenases. Acute anti-inflammatory doses of flosulide and indomethacin were determined on carrageenan paw edema and its effects on renal plasma flow (RPF) and glomerular filtration rate (GFR) were studied in normovolemic and hypovolemic rats. In normovolemic rats, flosulide increased RPF and GFR (25 mg/kg) and indomethacin (5-10 mg/kg) was without effect. Volume-depleted rats were obtained by oral furosemide (32 mg/kg), urinary eicosanoids were determined. After furosemide, plasma volume, RPF and GFR and PGE2 decreased. Treatment of hypovolemic rats with flosulide (5-25 mg/kg) or indomethacin 10 mg/kg reduced RPF and GFR. Flosulide at 5 mg/kg reduced 6-keto-PGF1alpha whereas at 25 mg/kg and after indomethacin at 10 mg/kg a fall in 6-keto-PGF1alpha and TXB2 appeared. Our data suggest that acute COX-2 selective inhibition may alter renal function.
Turull
A
A
Department de Fisiologia-Divisió IV, Facultat de Farmàcia, Barcelona, Spain.
Piera
C
C
Queralt
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D015232:Dinoprostone / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007189:Indans / Q000633:toxicity*; D007213:Indomethacin / Q000633:toxicity; D007527:Isoenzymes / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008565:Membrane Proteins; D010953:Plasma Volume / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017595:Renal Plasma Flow / Q000187:drug effects*; D013929:Thromboxane B2 / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D007527:Isoenzymes; D008565:Membrane Proteins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C059178:flosulide; D015232:Dinoprostone; D007213:Indomethacin