Effects of Pinacidil and Cromakalim (BRL 34915) On Bladder Function in Rats with Detrusor Instability

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Abstract
Normal rats as well as rats with bladder hypertrophy secondary to outflow obstruction were investigated cystometrically before and after administration of the potassium channel openers pinacidil or cromakalim one mg./kg. orally. In normal rats cromakalim decreased micturition pressure by 15 .+-. 6%. A diminished micturition pressure was also seen after pinacidil (by 18 .+-. 8%) but this did not achieve statistical significance. Further, no clear-cut effects on bladder capacity, residual volume, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension were seen in this group of rats neither in the presence of pinacidil nor cromakalim. Rats with bladder hypertrophy exhibited a significant bladder instability during cystometrical investigations. The mean amplitude of the spontaneous bladder contractions exceeded 20 cm. H2O prior to micturition. Administration of pinacidil and cromakalim decreased the spontaneous contractions to 26 .+-. 12% and 22 .+-. 7%, respectively, of that seen in the absence of the drugs. Furthermore, pinacidil decreased micturition pressure by 61 .+-. 12%. Also cromakalim decreased micturition pressure (by 27 .+-. 13%) but this effect did not achieve statistical significance. After both pinacidil and cromakalim these rats tended to develop residual urine. In accordance with the results in normal rats pinacidil and cromakalim showed no effects on bladder capacity, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension in rats with bladder hypertrophy. The findings of an almost complete disappearance of spontaneous bladder contractions in rats with bladder instability and a remaining voiding ability after administration of pinacidil or cromakalim suggest that potassium channel openers may be a therapeutic alternative in the treatment of bladder instability associated with outflow obstruction.