Treatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis.
Animals
Benzoates
/ pharmacology
Biphenyl Compounds
/ pharmacology
Celecoxib
/ pharmacology
Chronic Disease
Cystitis
/ drug therapy
Guanylate Cyclase
/ metabolism
Humans
Hydrocarbons, Fluorinated
/ pharmacology
Male
Pelvic Pain
Prostatitis
/ drug therapy
Rats
Rats, Sprague-Dawley
Soluble Guanylyl Cyclase
/ metabolism
Urinary Bladder
/ drug effects
BAY 60–2770
Celecoxib
Chronic pelvic pain syndrome
LUTS
Prostatitis
sGC activator
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
15 Jul 2022
15 Jul 2022
Historique:
received:
27
01
2022
revised:
17
05
2022
accepted:
19
05
2022
pubmed:
2
6
2022
medline:
18
6
2022
entrez:
1
6
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
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
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 35643304
pii: S0014-2999(22)00313-2
doi: 10.1016/j.ejphar.2022.175052
pii:
doi:
Substances chimiques
4-(((4-carboxybutyl) (2- (5-fluoro-2-((4'-(trifluoromethyl) biphenyl-4-yl)methoxy)phenyl)ethyl) amino)methyl)benzoic acid
0
Benzoates
0
Biphenyl Compounds
0
Hydrocarbons, Fluorinated
0
Guanylate Cyclase
EC 4.6.1.2
Soluble Guanylyl Cyclase
EC 4.6.1.2
Celecoxib
JCX84Q7J1L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
175052Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.