Effects of intravesical administration of the K+ channel opener, ZD6169, in conscious rats with and without bladder outflow obstruction.

Abstract

To investigate the urodynamic effects of the new K(ATP) channel opener, ZD6169, given intravesically, in rats with and without bladder outflow obstruction. Female, conscious Sprague-Dawley rats, normal or with bladder hypertrophy and overactivity secondary to bladder outflow obstruction, were given ZD6169 intravesically (10 or 100 ng./ml.), and intra-arterially (1 mg./kg.). Continuous cystometry was performed. In normal and obstructed rats, intravesical ZD6169 had similar, dose-dependent effects on bladder function. In obstructed rats, ZD6169 (100 ng./ml.) significantly decreased micturition pressure (17%), and increased bladder capacity (32%), micturition volume (18%), residual volume (145%), and inter-contraction interval (71%). There was a marked decrease in both frequency (40%) and amplitude (43%) of the spontaneous bladder activity. When given intra-arterially in obstructed rats ZD6169 increased bladder capacity (19%) and residual volume (47%) and decreased amplitude (51%), but not frequency, of the spontaneous bladder activity. In both normal and obstructed rats, intravesical ZD6169, at the investigated doses, significantly affected bladder function. In obstructed rats, the drug markedly reduced bladder overactivity. If the results have clinical validity, intravesical ZD6169 may offer an alternative way of treating bladder overactivity in selected patients.