Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites

Background & Aims: The critical role of cyclooxygenase (COX) products in ma intenance of renal function in cirrhosis with ascites discourages the use o f nonsteroidal anti-inflammatory drugs in this disease. The recent developm ent of selective COX-2 inhibitors opens new avenues for the use of these co mpounds in decompensated cirrhosis, The current study evaluates the effects of a selective COX-2 inhibitor (SC-236) on renal function in cirrhotic rat s with ascites, Methods: In protocol 1, urine volume, urinary excretion of sodium and prostaglandins, glomerular filtration rate, and renal plasma flo w were measured before and after administration of SC-236 (n = 12) or ketor olac (n = 10) to rats with cirrhosis, Protocol 2 was aimed at assessing the effects of COX inhibitors on renal water metabolism in 28 cirrhotic rats, Results: Administration of SC-236 to cirrhotic animals did not produce sign ificant renal effects, whereas administration of the nonselective COX-1/COX -2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, ur inary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism. Conclusions: These findin gs indicate that SC-236 does not significantly impair renal function in rat s with cirrhosis.