Abstract
Metabolic syndrome (MetS) is a risk factor for erectile dysfunction (ED), but the underlying mechanisms are unclear. The aims of this study were to determine the underlying mechanisms of metabolic syndrome-related ED (MED). Sprague Dawley (SD) rats were fed a high-fat diet for 6 months, and metabolic parameters were then assessed. An apomorphine test was conducted to confirm MED. Only rats with MED were administered an intracavernosal injection of either epidermal growth factor (EGF) or vehicle for 4 weeks. Erectile responses were evaluated by determining the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP). Levels of protein expression were examined by western blotting and immunohistochemistry. Body weight, fasting blood glucose, plasma insulin and plasma total cholesterol were increased in the MetS rats compared with those in control rats (each p < 0.05). The maximum ICP/MAP, total ICP/MAP and concentration of cyclic guanosine mono-phosphate (cGMP) were significantly decreased in MED rats (each p < 0.05). The expression levels of p110α, p-Akt1 (Tyr308)/Akt1 and p-eNOS (Ser1177)/eNOS were reduced in MED rats (each p < 0.05). Activation of the PI3K/Akt/eNOS signaling cascade (intracavernosal injection of EGF) reversed these changes (each p < 0.05). The present study demonstrates that downregulation of the PI3K/Akt/eNOS signaling pathway is involved in MED.
Highlights
Erectile dysfunction (ED), which is the inability to achieve and sustain an erection sufficient for satisfactory vaginal intercourse, is a common clinical condition that affects quality of life[1]
Partial but significant recovery of erectile function was observed in the epidermal growth factor (EGF)-treated groups compared with the metabolic syndrome-related ED (MED) group, as reflected by significantly higher max intracavernosal pressure (ICP)/mean arterial blood pressure (MAP) and total ICP/MAP ratios in response to cavernous nerve electrical stimulation (p < 0.05)
We demonstrated that EGF contributes to penile erection via endothelial nitric oxide synthase (eNOS) activation in a phosphatidylinositol 3-kinase (PI3K)/ Akt-dependent manner in MED rats
Summary
Erectile dysfunction (ED), which is the inability to achieve and sustain an erection sufficient for satisfactory vaginal intercourse, is a common clinical condition that affects quality of life[1]. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling pathway is one of the main regulatory networks in the cell and influences almost all cellular activities, including replication, growth, metabolism, movement and differentiation. Other studies revealed that Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection[19,20]. Wen et al demonstrated that the A2B adenosine receptor contributes to penile erection via PI3K/Akt signaling-mediated eNOS activation[21]. The role of the PI3K/Akt/eNOS signaling pathway in MED remains to be elucidated. The aims of the present study were to determine the effect of the PI3K/Akt/eNOS signaling pathway on erectile function in a rat in vivo model of MED and to suggest a potential novel treatment strategy for MED
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
