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 cyclo-oxygenase (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-I (COX-1) and cyclo-oxygenase-2 (COX-2) mediate
prostanoids synthesis and contribute to the inflanunatory process. However, it is generally
assumed that NSAIDs anti-inflammatory and analgesic activity is mediated via Cox-2 inhibition
while inhibition of Cox-I is thought to be responsible for the gastric toxicity and bleeding
complications. It is unclear whether NSA1D-induced renal toxicity is attributable to inhibition of
Cox-I 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 hernodynamics and tubular excretion. Thus, changes in mean arterial
pressure (MAP), renal blood flow (RBF),. glomerular filtration rate (GFR) urine volume and
urinary Na+ and K+ excretion ratio, hematocrite value, serum Na+ , K+, urea and creatinine
concentrations were all detected after 1M injection of rofecoxib (1.0 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
Na+ and K+ excretion. Indomethacin but not rofecoxib reduced RBF and GFR. No significant
change was observed in MAP, hematocrite value or serum Na+. 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 RBF and GFR is caused
by the blockade of Cox-I. COX-2 inhibitors should be used with caution since they are, like
traditional NSAIDS, can induce renal function impairment. |
