Effect of diltiazem on in vitro rabbit bladder function.
The relationship between extracellular calcium and urinary bladder function was investigated by studying the effect of the specific calcium antagonist diltiazem on the functional ability of the in vitro whole rabbit urinary bladder to empty in response to pharmacological stimulation. The bladder was found to require an extracellular calcium concentration of 4.5 X 10(-4) M to elicit near complete cholinergic-mediated emptying. Diltiazem (1 X 10(-6) - 1 X 10(-4) M) inhibition of bladder function was competitively antagonized by increasing the extracellular calcium concentration (0.45 X 10(-4) - 3.6 X 10(-4) M). In the absence of diltiazem, alterations in the extracellular calcium concentration between 0.45 X 10(-4) and 3.6 X 10(-4) M had no significant effects on bladder response to bethanechol. KCl-mediated bladder emptying was significantly more sensitive to diltiazem inhibition than was bethanechol-stimulated emptying. Even at the intermediate diltiazem concentration of 1 X 10(-5) M, increasing the extracellular calcium concentration did not completely reverse the inhibitory effect of diltiazem on bladder response to KC1. These findings are consistent with the hypothesis that diltiazem at low concentrations may inhibit extracellular calcium influx while at higher concentrations translocation of intracellular stores of calcium may be inhibited as well. The study also suggests that diltiazem is capable of inhibiting urinary bladder function and deserves further consideration as a possible therapeutic agent in certain forms of urinary bladder dysfunction.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001626:Bethanechol Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects*
D001552:Benzazepines; D001626:Bethanechol Compounds; D011189:Potassium Chloride; D004110:Diltiazem; D002118:Calcium