Neurovascular dysfunction associated with erectile dysfunction persists after long‐term recovery from simulations of weightlessness and deep space irradiation

Abstract There has been growing interest within the space industry for long‐duration manned expeditions to the Moon and Mars. During deep space missions, astronauts are exposed to high levels of galactic cosmic radiation (GCR) and microgravity which are associated with increased risk of oxidative stress and endothelial dysfunction. Oxidative stress and endothelial dysfunction are causative factors in the pathogenesis of erectile dysfunction, although the effects of spaceflight on erectile function have been unexplored. Therefore, the purpose of this study was to investigate the effects of simulated spaceflight and long‐term recovery on tissues critical for erectile function, the distal internal pudendal artery (dIPA), and the corpus cavernosum (CC). Eighty‐six adult male Fisher‐344 rats were randomized into six groups and exposed to 4‐weeks of hindlimb unloading (HLU) or weight‐bearing control, and sham (0Gy), 0.75 Gy, or 1.5 Gy of simulated GCR at the ground‐based GCR simulator at the NASA Space Radiation Laboratory. Following a 12–13‐month recovery, ex vivo physiological analysis of the dIPA and CC tissue segments revealed differential impacts of HLU and GCR on endothelium‐dependent and ‐independent relaxation that was tissue type specific. GCR impaired non‐adrenergic non‐cholinergic (NANC) nerve‐mediated relaxation in the dIPA and CC, while follow‐up experiments of the CC showed restoration of NANC‐mediated relaxation of GCR tissues following acute incubation with the antioxidants mito‐TEMPO and TEMPOL, as well as inhibitors of xanthine oxidase and arginase. These findings indicate that simulated spaceflight exerts a long‐term impairment of neurovascular erectile function, which exposes a new health risk to consider with deep space exploration.