Sub-chronic restraint stress suppresses sexual potency and erection efficiency by targeting the hypothalamic-pituitary-testicular axis and the NO/cGMP/PDE5α pathway in adult rats.

Introduction: Male sexual potency and vigor are a complex neuroendocrine process and an important component of well-being. Psychological stress is one of the leading causes of male impotence worldwide. Therefore, to better understand the effects of psychological stress on male sexual potency, vigor, and the physiology of erection, we used the rat restraint stress (RS) model, which can most aptly simulate psychological stress. Methods: Adult male SD rats were exposed to RS for 1.5 or 3 hours/day for 30 days. Neuromodulators and hormones of sexual potency and penile erection were quantified using ELISA kit. The histoarchitecture of the penis was examined using Masson trichrome staining. Immunoblotting and immunofluorescence were used to assess the expression and immunolocalization patterns of penile erection markers. To assess sexual potency and vigor, a non-contact erection and a copulatory test were performed. Results: RS exposure decreased the circulatory levels of gonadotropins and testosterone while increasing the serum corticosterone level. RS exposure altered the histomorphology of the penis by decreasing the smooth muscle/collagen ratio and increasing oxidative stress in penile tissue. Furthermore, RS adversely affected NO availability for penile erection by decreasing the neurotransmitter acetylcholine and other erection facilitatory markers such as p-Akt, nNOS, eNOS, and cGMP, while increasing the inhibitory marker PDE5 alpha in the penis. RS exposure significantly reduced the frequencies of mount, intromission and ejaculation, whereas it prolonged sexual exhaustion by increasing latencies of postejaculatory mount, intromission, and ejaculation. Conclusion: The current findings suggest that psychological stressors, such as restraint stress, cause erectile dysfunction in adult male rats by modulating the hypothalamic-pituitary-testicular axis, oxidative balance, penile fibrosis, and the NO/cGMP/PDE5 alpha pathway of penile erection.