Sex-Specific Cardiovascular Adaptations to Simulated Microgravity in Sprague-Dawley Rats

Abstract Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffness in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) for 14 days. Pulse wave velocity (PWV) was greater in the aortic arch of females after HLU versus control females. HLU had no effect on aortic PWV in males. Aortic α smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex following HLU. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but were not altered in males. These changes in HLU females were associated with lower aortic PPARγ and increased oxidative stress markers in association with diastolic dysfunction. GPER agonist G1 prevented the increase in PWV and 8-hydroxy-2'-deoxyguanosine without altering PPARγ or p47phox in HLU females. This study highlights sex-specific vascular adaptations to the state of simulated microgravity.