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.