EFFECT OF THE SELECTIVE COX 2 INHIBITOR, ROFECOXIB VERSUS THE NON-SELECTIVE COX INHIBITOR, INDOMETHACIN ON RENAL HEMODYNAMICS AND TUBULAR EXCRETION
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide. The mechanism through which NSAIDs provide analgesia and suppress inflammation is the inhibition of the enzyme cyclooxygenase (COX) with subsequent suppression of the prostanoids synthesis. The suppression of prostanoids synthesis can also produce gastric and renal toxicity, as well as impair normal platelet function. Two distinct but related enzymes. cyclo-oxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mediate prostanoids synthesis and contribute to the inflammatory process. However, it is generally assumed that NSAIDs anti-inflammatory and analgesic activity is mediated via COX-2 inhibition while Inhibition of COX-] is thought to be responsible for the gastric toxicity and bleeding complications. It is unclear whether NSAID-induced renal toxicity is attributable to inhibition of COX-1 or COX-2. The present study was designed to compare the effect of chronic administration of selective COX-2 inhibitor. rofecoxib with that of the non selective COX inhibitor, indomethacin on renal hemodynamics and tubular excretion. Thus, changes in mean arterial pressure (MAP), renal blood flow (RBF), glomerular filtration rate (Gilt), urine volume and urinary NC and IC+ excretion ratio, hematocrite value, serum NC ,K* ,urea and creatinine concentrations were all detected after IM injection of rofecoxib (1 umol/kg), indomethacin (3 umol/kg) or the vehicle for three weeks. Results from the present study showed that three weeks treatment with both indomethacin and rofecoxib induced a decrease in urine volume and NC and K` excretion. lndomethacin but not rofecoxib reduced RBF and GFR. No significant change was observed in MAP, hematocrite value or serum Na. serum. Serum K+, urea and creatinine levels were all elevated suggesting impairment in the renal functions. It seems likely that COX-2 inhibition causes acute salt and water retention, whereas the decline in RT3F and Gilt is caused by the blockade of COX-1. COX-2 inhibitors should be used with caution since they are, like traditional NSAIDs, can induce renal function impairment.