Renal effects of cyclooxygenase-2 inhibition in fetal lambs

We used late gestation fetal lambs to examine the effects of a selective COX-2 inhibitor (celecoxib) on fetal renal function. After a 2-hour baseline period, each fetus was exposed to either saline (control, n = 10), 'low-dose' celecoxib (plasma concentration 0.47 microg/ml, n = 4), or 'high-dose' celecoxib (1.4 microg/ml, n = 8) during a 5-hour study period. High-dose celecoxib (but not low-dose celecoxib) caused a significant decrease in urine volume, free water clearance, arterial pH, and an increase in blood lactate compared with the control group. There were no significant differences in creatinine clearance, fractional excretion of sodium and potassium, or in renal blood flow between the 3 groups. These effects are similar to those reported for the nonselective COX-1/-2 inhibitor, indomethacin. COX-2 appears to play an important role in promoting free water excretion in the fetal lamb.