Treatment with the soluble guanylate cyclase activator BAY 60–2770 normalizes bladder function in an in vivo rat model of chronic prostatitis

Ozgu Aydogdu, Fernando Perez, Patrik Aronsson, Pinar Uyar Gocun, Thomas Carlsson, Peter Sandner, Bhavik Patel, Michael Winder

Research output: Contribution to journalArticlepeer-review

Abstract

Background and purpose
Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60–2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS.

Experimental approach
Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8–20, the rats were treated with either dimethylsulphoxide (DMSO; vehicle), celecoxib, BAY 60–2770 or a combination of celecoxib and BAY 60–2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathologically.

Key results
Induction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60–2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60–2770, either alone or in combination with celecoxib. The immunohistochemical analysis showed signs of prostate inflammation, but not bladder inflammation.

Conclusion and implications
Induction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60–2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.
Original languageEnglish
Article number175052
Number of pages10
JournalEuropean Journal of Pharmacology
Volume927
DOIs
Publication statusPublished - 26 May 2022

Keywords

  • Chronic pelvic pain syndrome
  • Prostatitis
  • LUTS
  • BAY 60–2770
  • sGC activator
  • Celecoxib

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