Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis
Aim:: Examine how innate bladder contractility and corresponding receptor expression was affected by chronic prostatitis (CP) and how treatment with the soluble guanylate cyclase (sGC) activator BAY 60-2770 influenced this. Methods:: To create a functional model for CP, 24 male Sprague-Dawley rats w...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Continence |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772973722009961 |
| _version_ | 1797978689030324224 |
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| author | Ozgu Aydogdu Fernando Perez Jan Rataj Felicia Nilsson Patrik Aronsson Thomas Carlsson Peter Sandner Bhavik Patel Gunnar Tobin Michael Winder |
| author_facet | Ozgu Aydogdu Fernando Perez Jan Rataj Felicia Nilsson Patrik Aronsson Thomas Carlsson Peter Sandner Bhavik Patel Gunnar Tobin Michael Winder |
| author_sort | Ozgu Aydogdu |
| collection | DOAJ |
| description | Aim:: Examine how innate bladder contractility and corresponding receptor expression was affected by chronic prostatitis (CP) and how treatment with the soluble guanylate cyclase (sGC) activator BAY 60-2770 influenced this. Methods:: To create a functional model for CP, 24 male Sprague-Dawley rats were intraprostatically injected with either zymosan or saline, serving as control. After a recovery period, the rats were treated with either BAY 60-2770 or dimethyl sulfoxide (DMSO; vehicle) on days 8–20. Urine samples were collected for measurement of ATP. On day 21, the bladder was excised and contractile responses to electrical field stimulation (EFS), methacholine, ATP and nitric oxide (NO) were examined in an in vitro organ bath. Subsequently, the expression of purinergic (P2X1 & P2X3) and muscarinic (M3) receptors as well as sGC was examined immunohistochemically. Results:: Induction of CP led to significantly attenuated purinergic bladder contractions, which were normalized by treatment with BAY 60-2770. Induction of CP did not alter the contractile bladder responses to EFS, methacholine or NO. However, treatment with BAY 60-2770 led to significantly increased contractile bladder responses to EFS and MeCh and significantly enhanced relaxatory nitrergic responses. There were no significant differences between the groups regarding purinergic or cholinergic receptor expression, however treatment with BAY 60-2770 led to attenuated expression of sGC in the urothelium. Conclusion:: Taken together, these findings indicate that drugs targeting the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway may be a promising option to restore alterations in bladder contractility that arise due to CP. |
| first_indexed | 2024-04-11T05:28:05Z |
| format | Article |
| id | doaj.art-4a711952ad5f411d9ab6fe761b1c601d |
| institution | Directory Open Access Journal |
| issn | 2772-9737 |
| language | English |
| last_indexed | 2024-04-11T05:28:05Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Continence |
| spelling | doaj.art-4a711952ad5f411d9ab6fe761b1c601d2022-12-23T04:43:00ZengElsevierContinence2772-97372022-12-014100520Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitisOzgu Aydogdu0Fernando Perez1Jan Rataj2Felicia Nilsson3Patrik Aronsson4Thomas Carlsson5Peter Sandner6Bhavik Patel7Gunnar Tobin8Michael Winder9Department of Pharmacology, University of Gothenburg, Gothenburg, SwedenDepartment of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UKDepartment of Pharmacology, University of Gothenburg, Gothenburg, SwedenDepartment of Pharmacology, University of Gothenburg, Gothenburg, SwedenDepartment of Pharmacology, University of Gothenburg, Gothenburg, SwedenDepartment of Pharmacology, University of Gothenburg, Gothenburg, SwedenBayer AG Pharmaceuticals, Wuppertal, Germany; Institute of Pharmacology, Hannover Medical School, Hannover, GermanyDepartment of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UKDepartment of Pharmacology, University of Gothenburg, Gothenburg, SwedenDepartment of Pharmacology, University of Gothenburg, Gothenburg, Sweden; Correspondence to: Medicinaregatan 13, 405 30, Göteborg, Sweden.Aim:: Examine how innate bladder contractility and corresponding receptor expression was affected by chronic prostatitis (CP) and how treatment with the soluble guanylate cyclase (sGC) activator BAY 60-2770 influenced this. Methods:: To create a functional model for CP, 24 male Sprague-Dawley rats were intraprostatically injected with either zymosan or saline, serving as control. After a recovery period, the rats were treated with either BAY 60-2770 or dimethyl sulfoxide (DMSO; vehicle) on days 8–20. Urine samples were collected for measurement of ATP. On day 21, the bladder was excised and contractile responses to electrical field stimulation (EFS), methacholine, ATP and nitric oxide (NO) were examined in an in vitro organ bath. Subsequently, the expression of purinergic (P2X1 & P2X3) and muscarinic (M3) receptors as well as sGC was examined immunohistochemically. Results:: Induction of CP led to significantly attenuated purinergic bladder contractions, which were normalized by treatment with BAY 60-2770. Induction of CP did not alter the contractile bladder responses to EFS, methacholine or NO. However, treatment with BAY 60-2770 led to significantly increased contractile bladder responses to EFS and MeCh and significantly enhanced relaxatory nitrergic responses. There were no significant differences between the groups regarding purinergic or cholinergic receptor expression, however treatment with BAY 60-2770 led to attenuated expression of sGC in the urothelium. Conclusion:: Taken together, these findings indicate that drugs targeting the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway may be a promising option to restore alterations in bladder contractility that arise due to CP.http://www.sciencedirect.com/science/article/pii/S2772973722009961sGC activatorChronic prostatitisUrinary bladderOrgan bathIn vitroAnimal model |
| spellingShingle | Ozgu Aydogdu Fernando Perez Jan Rataj Felicia Nilsson Patrik Aronsson Thomas Carlsson Peter Sandner Bhavik Patel Gunnar Tobin Michael Winder Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis Continence sGC activator Chronic prostatitis Urinary bladder Organ bath In vitro Animal model |
| title | Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis |
| title_full | Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis |
| title_fullStr | Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis |
| title_full_unstemmed | Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis |
| title_short | Treatment with the soluble guanylate cyclase activator BAY 60-2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis |
| title_sort | treatment with the soluble guanylate cyclase activator bay 60 2770 restores in vitro bladder contractile responses in a rat model of chronic prostatitis |
| topic | sGC activator Chronic prostatitis Urinary bladder Organ bath In vitro Animal model |
| url | http://www.sciencedirect.com/science/article/pii/S2772973722009961 |
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