Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter

Article Article scientifique Article Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter eng 2000 author Mastrangelo Domenico 29705 author Wisard Martin 89060 author Rohner Stéphane 69636 author Leisinger Hélène 95615 author Iselin Christophe 29699 376-382 10.1007/s002400000139 11221916 0300-5623 Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first-line treatment of renal colic. Their action has been ascribed to the inhibition of renal prostaglandin synthesis, which decreases renal blood flow and diuresis, and consequently lowers the pressure in the renal pelvis and ureter. However, the effects of NSAIDs on induced contractions of ureteral smooth muscle have received little attention. Also, there is a lack of clinically relevant spasmolytic drugs for the ureter. Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30 microM) and neurokinin A (0.03-10 microM) induced reproducible concentration-dependent contractions, which were inhibited by diclofenac and NS-398 (10-300 microM) in a concentration-dependent manner. The sensitivity of neurokinin A-induced contractions to diclofenac was 3-4 times greater than that of the amines. Depending on the concentration, inhibition ranged between 25 and 96% of the initially induced contractile activity. In the presence of inhibitors, supramaximal concentrations of agonists were unable to trigger recuperation of the initially induced contractions. Prostaglandin F2alpha did not reverse the effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS-398 from the organ baths showed that the inhibition was totally reversible. Thus, the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS-398 are almost equipotent in reducing agonist-induced contractions in the isolated porcine ureter. Although the clinical relevance of this spasmolytic effect remains to be demonstrated, the data suggest that patients suffering from renal colic may benefit not only from the anti-diuretic and analgesic effects of diclofenac, but also from its potential spasmolytic properties. Moreover, selective COX-2 inhibitors may have clinical potential, as they may cause fewer side effects. Animals Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors/pharmacology Diclofenac/pharmacology Free Radical Scavengers/pharmacology Isoenzymes/antagonists & inhibitors/metabolism Muscle Contraction/drug effects/physiology Muscle, Smooth/physiology Neurokinin A/pharmacology Nitrobenzenes/pharmacology Norepinephrine/pharmacology Organ Culture Techniques Prostaglandin-Endoperoxide Synthases/metabolism Serotonin/pharmacology Sulfonamides/pharmacology Swine Sympathomimetics/pharmacology Ureter/drug effects/physiology Dewey 617 57 Département de chirurgie 222 false 81 Groupe Iselin Christophe (urologie) 106 Urological research 28 6 caa6f249-4a66-4a17-9df9-9b914246979a Article (Published version) Restricted art%3A10.1007%2Fs002400000139.pdf 154046 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter	Urological research			2000	483	0

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Leisinger, Hélène