Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice

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dc.contributor.authorOlivencia Plaza, Miguel Ángel
dc.contributor.authorGil De Biedma Elduayen, Leticia
dc.contributor.authorGiménez Gómez, Pablo
dc.contributor.authorBianca Barreira
dc.contributor.authorArgentina Fernández
dc.contributor.authorJavier Angulo
dc.contributor.authorColado Megías, María Isabel
dc.contributor.authorO'Shea Gaya, María Esther
dc.contributor.authorPérez Vizcaíno, Francisco
dc.date.accessioned2024-04-22T09:05:25Z
dc.date.available2024-04-22T09:05:25Z
dc.date.issued2023-05-12
dc.description.abstract<jats:sec><jats:title>Background and purpose</jats:title><jats:p>Alcohol abuse has been associated with erectile dysfunction (ED), but the implicated molecular mechanisms are unresolved. This study analyses the role of alterations in soluble guanylyl cyclase (sGC) in ED.</jats:p></jats:sec><jats:sec><jats:title>Experimental approach</jats:title><jats:p>ED was analysed in adult male C57BL/6J mice subjected to the Chronic Intermittent Ethanol (CIE) paradigm. Erectile function was assessed in anaesthetised mice in vivo by evaluating intracavernosal pressure (ICP) and in vitro in isolated mice corpora cavernosa (CC) mounted in a myograph. Protein expression and reactive oxygen species were analysed by western blot and dihydroethidium staining, respectively.</jats:p></jats:sec><jats:sec><jats:title>Key results</jats:title><jats:p>In CIE mice, we observed a significant decrease in the relaxant response of the CC to stimulation of NO release from nitrergic nerves by electrical field stimulation, to NO release from endothelial cells by acetylcholine, to the PDE5 inhibitor sildenafil, and to the sGC stimulator riociguat. Conversely, the response to the sGC activator cinaciguat, whose action is independent of the oxidation state of sGC, was significantly enhanced in these CC. The responses to adenylyl cyclase stimulation with forskolin were unchanged. We found an increase in reactive oxygen species in the CC from CIE mice as well as an increase in CYP2E1 and NOX2 protein expression. In vivo pre‐treatment with tempol prevented alcohol‐induced erectile dysfunction.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and implications</jats:title><jats:p>Our results demonstrate that alcoholic mice show ED in vitro and in vivo due to an alteration in the redox state of sGC and suggest that sGC activators may be effective in ED associated with alcoholism.</jats:p></jats:sec>
dc.description.departmentDepto. de Farmacología, Farmacognosia y Botánica
dc.description.facultyFac. de Medicina
dc.description.fundingtypeAPC financiada por la UCM
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad (España)
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.sponsorshipMinisterio deSanidad, Servicios Sociales e Igualdad (España)
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipBanco Santander
dc.description.statuspub
dc.identifier.citationOlivencia, M. A., Gil deBiedma-Elduayen, L., Giménez-G omez, P., Barreira, B.,Fernández, A., Angulo, J., Colado, M. I., O'Shea, E., &Perez-Vizcaino, F. (2023). Oxidized soluble guanylyl cyclasecauses erectile dysfunction in alcoholic mice. British Journal ofPharmacology,180(18), 2361–2376.https://doi.org/10.1111/bph.16087
dc.identifier.doi10.1111/bph.16087
dc.identifier.issn0007-1188
dc.identifier.issn1476-5381
dc.identifier.officialurl10.1111/bph.16087
dc.identifier.urihttps://hdl.handle.net/20.500.14352/103306
dc.issue.number18
dc.journal.titleBritish Journal of Pharmacology
dc.language.isospa
dc.page.final2376
dc.page.initial2361
dc.publisherWiley
dc.relation.projectIDMICINN/PID2019-105847RB-I00
dc.relation.projectIDMINECO//PID2019-107363RB-I00
dc.relation.projectIDMSSSI/PNSD/2019I025
dc.relation.projectIDMSSSI/PNSD/2022I033
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu613.81-05
dc.subject.cdu615.212
dc.subject.ucmFarmacología (Medicina)
dc.subject.unesco3209 Farmacología
dc.titleOxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number180
dspace.entity.typePublication
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