Effects on bladder function of combining elocalcitol and tolterodine in rats with outflow obstruction

Tomi Streng, Karl Erik Andersson, Petter Hedlund, Christian Gratzke, Enrico Baroni, Daniele D'Ambrosio, Fabio Benigni

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To evaluate the effects of tolterodine on urodynamics in elocalcitol- or vehicle-treated rats with partial urethral obstruction (PUO). Materials and Methods After ethical approval, 20 female Sprague-Dawley rats were subjected to PUO and treated (gavage) for 14 days (once daily) with elocalcitol (75 Âμg/kg) or vehicle. Cystometries were performed on day 15 in awake rats before and after i.v. administration of tolterodine (1, 10 and 100 Âμg/kg). Results No differences in bladder weights or body/bladder weight ratios were noted between groups. Tolterodine dose-dependently increased micturition intervals and volumes and bladder capacity in both elocalcitol- (n= 11) and vehicle-treated rats (n= 9). In elocalcitol-treated rats, flow pressure (FP) was dose-dependently reduced (12-20%) by tolterodine, whereas no effect on FP was noted in vehicle-treated animals (P <0.05). Flow compliance (FC) was increased by tolterodine by 21-54% in vehicle-treated rats, and by 47-131% (P <0.05 vs vehicle) in elocalcitol-treated animals. Maximal tension vs bladder weight was improved in elocalcitol-treated rats in comparison to vehicle (P <0.05). The area under the curve (AUC) was reduced by tolterodine with 11-16% in vehicle-treated rats and 26-30% in elocalcitol -treated rats (P <0.05). Conclusions Elocalcitol-treatment improved the effects of tolterodine on bladder compliance at the start of flow. The effects of tolterodine on AUC suggest that elocalcitol exerts additional beneficial actions on PUO-induced functional changes during the filling phase of micturition. The reduction of FP and increase in FC by elocalcitol and tolterodine could have translational value and, if valid in humans, support combined therapy in benign prostatic obstruction (BPO)-related lower urinary tract symptoms (LUTS).

Original languageEnglish
JournalBJU International
Volume110
DOIs
Publication statusPublished - Jul 2012

Keywords

  • antimuscarinics
  • BXL628
  • partial urethral obstruction
  • vitamin D analogue

ASJC Scopus subject areas

  • Urology

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