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. |
