Renal hemodynamic effects of chronic ketorolac tromethamine treatment in aged lean and obese Zucker rats.
Ketorolac tromethamine is a relatively new non-steroidal anti-inflammatory drug (NSAID), with potent analgesic activity. Similar to other NSAIDs, ketorolac has the potential to impair renal function. To assess the renal hemodynamic impact of the ketorolac in aged lean and obese rats, ketorolac was orally administered to 46-week-old lean and obese Zucker rats for two weeks. Ketorolac was mixed with rat chow in a manner to provide a dose equivalent to 15 mg/kg body weight/day. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured under anesthesia by standard inulin and p-aminohippuric acid clearance method, respectively. Urinary prostaglandin (PG) E2 excretion was measured before and after ketorolac treatment. Ketorolac treatment significantly reduced obese rat GFR (0.47 +/- 0.08 vs 0.78 +/- 0.03 ml/min/g, p < 0.002) and ERPF (1.12 +/- 0.14 vs 2.36 +/- 0.26 ml/min/g, p < 0.001) relative to obese control rats. In comparison, ketorolac did not significantly alter lean rats GFR (0.77 +/- 0.04 vs 0.91 +/- 0.06 ml/min/g) or ERPF (1.92 +/- 0.20 vs 2.48 +/- 0.15 ml/min/g) relative to lean control rats. Chronic ketorolac treatment significantly reduced hematocrit by 20 and 30 percent in lean and obese rats relative to controls, respectively. The renal vascular resistance was significantly increased with ketorolac treatment in obese rats (36 +/- 4 vs 79 +/- 14 mmHg/ml/min, p < 0.001) but not lean rats (28 +/- 3 vs 38 +/- 5 mmHg/ml/min, NS) relative to corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Alavi
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FK
Department of Internal Medicine, University of South Dakota School of Medicine, Sioux Falls 57107-1570, USA.
Zawada
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ET
Hoff
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KK
D000375:Aging; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001835:Body Weight; D015232:Dinoprostone / Q000652:urine; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D020911:Ketorolac Tromethamine; D007668:Kidney / Q000187:drug effects*; D009765:Obesity / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D012079:Renal Circulation / Q000187:drug effects*; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D013997:Time Factors; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000633:toxicity; D014325:Tromethamine / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D014046:Tolmetin; D015232:Dinoprostone