Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo
Article first published online: 29 JAN 2009
2008 British Pharmacological Society
British Journal of Pharmacology
Volume 154, Issue 6, pages 1297–1307, July 2008
How to Cite
Chaignat, V., Danuser, H., Stoffel, M. H., Z'Brun, S., Studer, U. E. and Mevissen, M. (2008), Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo. British Journal of Pharmacology, 154: 1297–1307. doi: 10.1038/bjp.2008.193
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received January 10, 2008, Revised February 27, 2008, Accepted April 15, 2008)
- ureter peristalsis;
- ureteric calculi
Background and purpose:
Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney.
Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry.
Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 × 10−11 M) than in distal specimens (EC50=7.4 × 10−10 M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney.
Conclusions and implications:
Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.
British Journal of Pharmacology (2008) 154, 1297–1307; doi:10.1038/bjp.2008.193; published online 26 May 2008