Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats

Abstract

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 PDE5α 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/PDE5α pathway of penile erection.

NaHS reverts chronic stress-induced cardiovascular alterations by reducing oxidative stress

“…Therefore, we measured the expression of eNOS and its phosphorylation; however, we did not observe changes in animals with chronic stress. Previous findings suggest that chronic stress decreases the endothelium eNOS expression in the thoracic aorta, 57 penis smooth muscle, 10 and hippocampus, 11 affecting NO production. An explanation of this difference between our findings and the abovementioned studies is the difference in the time of the restraint or the duration of the stressor between the protocols.…”

“…Indeed, the activity of superoxide dismutase and catalase, antioxidant enzymes, is decreased during chronic stress. 10,13,14 Conversely, the glutathione system is implicated in modulating oxidative stress because glutathione is a major antioxidant in the cellular defense against ROS. When the GSH 2 :GSSG ratio is decreased, it usually reflects an alteration in the redox environment.…”

“…Although corticosterone serves as a stress marker, 47 it has been reported that CRS affects corticosterone levels in a durationdependent manner. 10 Nevertheless, it is important to note that CRS remains a suitable model for assessing psychiatric disorders, such as depression-like behavior 36,38 and cardiovascular alterations induced by chronic stress. 12 Conversely, it has been reported that pretreatment with H 2 S donors decreased the corticosterone levels in animals with acute stress.…”

“…9 However, the underlying mechanisms of cardiovascular diseases induced by chronic stress are not fully understood. In this regard, chronic stress-induced impairments have been attributed to impaired endothelial nitric oxide synthetize (eNOS) 10,11 and increased reactive oxygen species (ROS) and lipid peroxidation in the serum 12 and brain of stressed animals. 13,14 Given that chronic stress is a significant risk factor for cardiovascular diseases in patients, [15][16][17] it is crucial to explore potential therapeutic agents that can reverse chronic stressinduced cardiovascular alterations, such as H 2 S, a gasotransmitter involved in cardiovascular regulation.…”

“…9 However, the underlying mechanisms of cardiovascular diseases induced by chronic stress are not fully understood. In this regard, chronic stress–induced impairments have been attributed to impaired endothelial nitric oxide synthetize (eNOS) 10,11 and increased reactive oxygen species (ROS) and lipid peroxidation in the serum 12 and brain of stressed animals. 13,14…”