The Impact of Long‐Duration Exposure to Microgravity and Galactic Cosmic Radiation on Corpus Cavernosum Function

Abstract

During spaceflight missions, astronauts are exposed to an extreme environment with high levels of radiation and microgravity, which negatively influence the cardiovascular system. With an increased development in space exploration and growing interest in manned missions to mars, it is of high importance to evaluate the health risks associated with long‐duration spaceflights. The increased risk of oxidative stress and inflammatory damage post‐spaceflight has been associated with cardiovascular dysfunction, but little is known about the influence of space exposure on erectile function, which is a critical component for quality of life in men. The purpose of this investigation was to determine the influence of long‐duration spaceflight on corpus cavernosum (CC) function. 86 adult male Sprague‐Dawley rats were randomized into 6 different groups with half of them enduring 4‐weeks of hindlimb unloading (HLU), and exposed to sham, 0.75Gy or 1.5Gy of simulated galactic cosmic radiation at the Ground‐based GCR Simulator at the NASA Space Radiation Laboratory (NSRL). Following a 6–9‐month recovery the rats were sacrificed, and CC tissue segments were harvested and mounted into a muscle strip myograph system for ex vivo functional assessment. CC reactivity to six 10‐s,30V‐electric field stimulations with progressive frequencies in the range of 1‐32 Hz targeting the non‐adrenergic non‐cholinergic (NANC) stimulation was assessed. The effects of HLU and radiation were determined by two‐way repeated measures ANOVA. High levels of radiation significantly decreased NANC‐mediated relaxation of the CC. Treatment with nitric oxide synthase (NOS) inhibitor L‐NAME completely inhibited tissue response to electric stimulation, showing that the relaxation was mainly driven by nitric oxide. Incubation of the CC tissue with the xanthine oxidase inhibitor allopurinol, the mitochondria‐targeted antioxidant mito‐TEMPO, and the superoxide dismutase (SOD) mimetic TEMPOL increased the relaxation response of the erectile tissue for the groups exposed to radiation, with little or opposite effect on the groups under no radiation exposure. Upon treatment with the Arginase inhibitor S‐(2‐boronoethyl)‐l‐cysteine (BEC), CC tissue for the groups under radiation exposure showed a significant improvement in relaxation under NANC electric field stimulation. Comparably, western blot analysis showed increased levels of oxidative stress and lipid peroxidation in the corpus cavernosum on the groups under radiation exposure by assessment of 4‐hydroxynonenal (HNE), as well as higher levels of arginase 1 and 2. This information suggests that increased oxidative stress from radiation exposure in long spaceflight trips impairs corpus cavernosum vasoreactivity and exposes new factors to consider with space exploration to ensure that astronauts can return to normal life after long trips in space.