SELECTIVE CYCLOOXYGENASE-2 INHIBITORS REDUCE URETERAL CONTRACTION IN VITRO: A BETTER ALTERNATIVE FOR RENAL COLIC?

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Abstract
To quantitate the effects of a selective cyclooxygenase (COX)-2 inhibitor, NS-398, on porcine and human ureteral contractility in vitro. This study was performed in 3 distinct groups. In group 1, segments of ureter were obtained from freshly sacrificed domestic swine. Sections were isolated and suspended longitudinally. Twenty-four ureteral segments were treated with either indomethacin (a nonselective COX inhibitor), NS-398 (selective COX-2 inhibitor), or DMSO (control). Spontaneous contractions were then recorded in each group. In group 2, fifteen segments of human ureter were obtained from patients undergoing donor nephrectomy or ureteral reimplantation. Segments were isolated and suspended as above, and treated with either indomethacin, NS-398, or DMSO. In group 3, eighteen sections of human ureter obtained from donor nephrectomy patients were passively sensitized for 20 hours in ragweed allergic donor serum. Ureteral segments were then treated with either indomethacin, NS-398 or DMSO, and then the segments were subsequently exposed to ragweed antigen and contractions were subsequently recorded. In group 1, the average time to 100% inhibition of spontaneous contraction was 48.8 minutes (S.E.M. = 7.9) for indomethacin, 65.7 minutes (S.E.M. 6.7) for NS-398, and beyond 150 minutes for DMSO. The percent reduction was 100% for indomethacin (S.E.M. = 0), 92.5% for NS-398 (S.E.M. 4.9%), and 52.9% for DMSO (s.e.m. = 10.8%). In group 2, the average time to 100% inhibition was 29 minutes (S.E.M. = 10.4) for indomethacin, 21 minutes (S.E.M. 4.8) for NS-398, and beyond 150 minutes for DMSO. The percent reduction was 100% for indomethacin (S.E.M. = 0), 100% (S.E.M. = 0) for NS-398, and 20% (S.E.M. = 12%) for DMSO. In group 3, ragweed sensitized ureters treated with DMSO (control group) contracted an average maximum of 10 times per 5 minutes. Antigen failed to induce contractions of sensitized tissues treated with indomethacin or NS-398. A selective COX-2 inhibitor (NS-398) reduces ureteral contractility as effectively as indomethacin (a nonselective COX inhibitor) in both porcine and human ureteral segments in vitro (p <0.05). Selective COX-2 inhibitors may have significant clinical potential in treating renal colic as they cause less gastric ulceration.