Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo.
OBJECTIVE
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.


METHODS
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.


RESULTS
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 x 10(-11) M) than in distal specimens (EC50=7.4 x 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
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.
Chaignat
V
V
Division of Veterinary Pharmacology & Toxicology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty Berne, University of Berne, Berne, Switzerland.
Danuser
H
H
Stoffel
M H
MH
Z'brun
S
S
Studer
U E
UE
Mevissen
M
M
D000368:Aged; D000818:Animals; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D014513:Ureter / Q000187:drug effects*; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000503:physiopathology; D000096926:Benzenesulfonamides
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D007555:Isoxazoles; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides