A comparative in vitro study to determine the beneficial effect of calcium-channel and alpha(1)-adrenoceptor antagonism on human ureteric activity.
OBJECTIVE
To compare the in vitro human ureteric muscle response to calcium-channel and alpha-adrenoceptor antagonists, to determine the promoting factor for stone passage. Clinical trials suggest that stone passage in renal colic can be promoted by ureteric relaxation using these agents, however nonsteroidal anti-inflammatory drugs appear to reduce ureteric activity in vitro but do not promote stone passage when used in clinical trials.


METHODS
Human ureteric muscle strips were used to record the effect that each drug had on muscle tone in vitro. The ureter was obtained at open nephrectomy or cystectomy. Potassium-enriched Krebs' solution was used to evoke maximal muscle tone, followed by adding each drug in increasing concentrations to determine the percentage reduction in tone. The drugs used to represent each group were nifedipine, 5-methylurapidil (5-MU) and diclofenac. In all, 201 ureteric strips were obtained from 39 patients.


RESULTS
At all drug concentrations, the in vitro relaxant effect of nifedipine and 5-MU was greater than that of diclofenac. At 10(-5) M the median reduction in proximal and distal ureteric tone to diclofenac, nifedipine and 5-MU were 18%, 5% and 47%, vs 57%, 33% and 65%, respectively.


CONCLUSIONS
Nifedipine and 5-MU produced greater ureteric relaxation in vitro than diclofenac; they predominantly relax distal ureter. This suggests that a reduction in ureteric muscle tone, as opposed to complete ablation of activity, might be the promoting factor for stone passage.
Davenport
Kim
K
Bristol Urological Institute, Bristol, UK.
Timoney
Anthony G
AG
Keeley
Francis X
FX
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D010879:Piperazines; D004008:Diclofenac; C057446:5-methylurapidil; D009543:Nifedipine