The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

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dc.authoriduyanikgil, Yigit/0000-0002-4016-0522
dc.contributor.authorOlukman, Murat
dc.contributor.authorCan, Cenk
dc.contributor.authorUlker, Sibel
dc.contributor.authorUyanikgil, Yigit
dc.contributor.authorCavusoglu, Turker
dc.contributor.authorDuzenli, Neslihan
dc.contributor.authorCoskunsever, Deniz
dc.date.accessioned2025-03-20T09:51:13Z
dc.date.available2025-03-20T09:51:13Z
dc.date.issued2025
dc.departmentİzmir Bakırçay Üniversitesi
dc.description.abstractObjective: This study aimed to investigate the effects of treatment with palosuran, a urotensin receptor blocker, on molecular changes in the corpora cavernosa (CC) in diabetic rats. Methods: Streptozotocin-induced diabetic rats were treated with palosuran 300 mg/kg per day for 6 weeks. Contraction of CC induced by potassium chloride, phenylephrine, and NG-nitro-L-arginine methyl ester and relaxation of CC induced by electrical field stimulation (EFS) and sodium nitroprusside (SNP) (endothelium-dependent and endothelium-independent stimuli, respectively), and Y-27632 (Rho-kinase inhibitor) were examined in organ baths. Direct contraction or relaxation induced by palosuran and urotensin-II (U-II) were also evaluated. The expression levels of nitric oxide synthetases (NOSs), RhoA, oxidative stress regulators, and U-II were analyzed by Western blotting or immunohistochemistry. Results: Induction of diabetes in rats resulted in the decreased relaxant response to SNP, decreased pD2 value of SNP, attenuated relaxant response to Y-27632 as well as the decreased RhoA expression in CC. Palosuran treatment of diabetic rats reversed all of these parameters; however, it further impaired the already weakened relaxation of diabetic CC in response to EFS. Although induction of diabetes did not change U-II expression in CC significantly, palosuran treatment reduced U-II expression in diabetic CC. The expression level of nNOS was lowered in diabetic CC; however, palosuran treatment did not change the decreased the neuronal NOS expression. In vitro exposure of diabetic CC strips to palosuran produced a direct relaxant response. Conclusion: Palosuran treatment did not affect the expression of NOSs or reduce nitrergic conduction induced by EFS stimulation in diabetic CC. However, while directly triggering a relaxant response, it did not induce a prominent contraction either by decreasing U-II expression, or increasing the sensitivity of CC to nitric oxide which suggested that palosuran has the potential to support erectile function. Further and comprehensive studies are required to clarify this issue. (c) 2025 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [110S016]; TUBITAK
dc.description.sponsorshipThis study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 110S016; the authors thank to TUBITAK for their supports. We would also like to thank Prof. Marc Inglarz and Actelion Company (Basel, Switzerland) for providing the palosuran used in this study.
dc.identifier.doi10.1016/j.ajur.2024.02.010
dc.identifier.endpage126
dc.identifier.issn2214-3882
dc.identifier.issn2214-3890
dc.identifier.issue1
dc.identifier.pmid39990066
dc.identifier.scopus2-s2.0-85210945523
dc.identifier.scopusqualityQ2
dc.identifier.startpage116
dc.identifier.urihttps://doi.org/10.1016/j.ajur.2024.02.010
dc.identifier.urihttps://hdl.handle.net/20.500.14034/2473
dc.identifier.volume12
dc.identifier.wosWOS:001420767200001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Singapore Pte Ltd
dc.relation.ispartofAsian Journal of Urology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250319
dc.subjectCorpora cavernosa
dc.subjectDiabetes mellitus
dc.subjectExperimental
dc.subjectErectile dysfunction
dc.subjectNitric oxide
dc.subjectPalosuran
dc.subjectRhoA
dc.subjectUrotensin II
dc.titleThe effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats
dc.typeArticle

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