Abstract
Men and women have different cardiovascular responses to spaceflight. We determined sex differences in arterial stiffness, an independent risk factor for cardiovascular dysfunction, in rats after the exposure to 14-days of simulated weightlessness via hindlimb unloading (HLU). Male and female Sprague-Dawley rats at 20 weeks of age were either tail suspended via HLU or remained full-weight bearing in similar cages. Female control rats had lower body weight compared with males. There was no significant effect of HLU on body weight in either male or female rats. Our data demonstrate that HLU increased aortic pulse wave velocity, an index of arterial stiffness, in female rats (2.7 fold vs. control female- adjusted for body weight, n=5-6), but not in males. HLU had no effect on the levels of structural proteins (alpha smooth muscle actin or myosin) in either female or male rats. The levels of G-protein-coupled estrogen receptor 1 (GPER) were lower in the thoracic aorta of female rats exposed to HLU compared with female controls (0.3±0.02 vs. 0.39±0.01 relative density, p<0.05, n=6-7); lower aortic GPER levels were associated with greater aortic media thickness (110.5±4.2 vs. 97.1±3.1 μm, p<0.05, n=5) and lower COX-2 protein levels (0.47±0.04 vs. 0.61±0.02 relative density, p<0.05, n=3-4). However, no differences in GPER, aortic media thickness, or COX-2 were observed in the aortas of male rats after HLU versus male controls. The administration of GPER agonist, G1 (400 ug/kg/day) prevented the increase in aortic pulse wave velocity in the intact females following HLU (2.2±0.2 vs. 9.7±1.8, p<0.05, n=4). Our data demonstrate sex differences in aortic stiffness in response to simulated microgravity. Since GPER has many protective actions in the cardiovascular system, a dysregulation of estrogen signaling may attenuate the protection of females from cardiovascular dysfunction following the exposure to spaceflight stressors.
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