Acute Effects of the Anti-Inflammatory Cyclooxygenase-2 Selective Inhibitor, Flosulide, on Renal Plasma Flow and Glomerular Filtration Rate in Rats |
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Authors: | Àngels Turull Carlos Piera Josep Queralt |
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Institution: | (1) Departament de Fisiologia-Divisió IV, Facultat de Farmàcia, Avda. Joan XXIII s/n, 08028 Barcelona, Spain;(2) Servei de Medicina Nuclear, Hospital Clinic i Provincial, Villarroel 170, 08036 Barcelona, Spain |
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Abstract: | 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-PGF1 whereas at 25 mg/kg and after indomethacin at 10 mg/kg a fall in 6-keto-PGF1 and TXB2 appeared. Our data suggest that acute COX-2 selective inhibition may alter renal function. |
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Keywords: | flosulide renal plasma flow (RPF) glomerular filtration rate (GFR) hypovolemia |
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