RT Journal Article
T1 Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice
A1 Olivencia Plaza, Miguel Ángel
A1 Gil De Biedma Elduayen, Leticia
A1 Giménez Gómez, Pablo
A1 Barreira, Bianca
A1 Fernández, Argentina
A1 Angulo, Javier
A1 Colado Megías, María Isabel
A1 O'Shea Gaya, María Esther
A1 Pérez Vizcaíno, Francisco
AB Background and purpose 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. Experimental approach 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.Key resultsIn 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.Conclusions and implicationsOur 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.
PB Wiley
SN 0007-1188
SN 1476-5381
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/103306
UL https://hdl.handle.net/20.500.14352/103306
LA spa
NO Olivencia, 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
NO Ministerio de Economía y Competitividad (España)
NO Ministerio de Ciencia e Innovación (España)
NO Ministerio deSanidad, Servicios Sociales e Igualdad (España)
NO European Commission
NO Universidad Complutense de Madrid
NO Banco Santander
DS Docta Complutense
RD 4 abr 2025