Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice

Abstract

Background and purposeAlcohol 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 approachED 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.

Genetic prediction of modifiable lifestyle factors for erectile dysfunction

“…A significant relationship between alcohol consumption and ED was observed in this study, which is consistent with previous studies. 22 We used drinks per week as a phenotype of alcohol intake in the research, which is defined as the average number of drinks a participant reported drinking each week, aggregated across all types of alcohol. If a study recorded binned response ranges, we used the midpoint of the range.…”

“…For example, if an individual reported 1 to 5 drinks per week, we assume that they drank 2.5 drinks per week on average. 15 Animal experiments have shown that 22 chronic exposure to alcohol reduces the relaxation response of the corpus cavernosum in vitro through neurogenic and endothelial pathways while attenuating the physiological process of increased pressure in the corpus cavernosum caused by bioelectrical conduction in vivo. Besides, frequent use of alcohol reduces libido and makes it difficult for men to achieve erections or orgasms.…”