Effects of microgravity exposure on arterial vascular stiffness.

摘要

Alterations in arterial stiffness play important roles in terrestrial-based cardiovascular pathologies and therefore may make significant contributions to microgravity-induced cardiovascular pathologies. It is hypothesized that there are changes in arterial stiffness due to microgravity exposure and that these changes have a significant role in microgravity-induced orthostatic intolerance (OI). Furthermore, it is hypothesized that the microgravity induced change in arterial stiffness is due to local remodeling within vascular wall. Lastly, it is hypothesized that the alterations in vascular stiffness are gender specific, which may represent one underlying cause for the gender disparity in the incidence of OI. These hypotheses were explored by using previously collected human astronaut data as well as actively utilizing two ground based models simulating microgravity exposure: head down tilt bedrest in humans and hindlimb unweighting in rats. Sensitive methods for measuring vascular stiffness were employed to monitor stiffness changes and molecular assays were used to discover any changes in arterial vascular wall composition after microgravity exposure. It was demonstrated that only orthostatically tolerant astronauts had an increase in vascular stiffness after microgravity exposure. Furthermore, the increased vascular stiffness due to microgravity exposure was shown to result from increased vessel wall collagen content and increased extracellular matrix crosslinking. Lastly, the gender studies demonstrated that females do not experience increases in vascular stiffness after microgravity exposure while males do. It appears that estrogen is primarily responsible for the observed female vascular stiffness response. It is clear that the increase in arterial stiffness after microgravity exposure contributes to the maintenance of orthostatic tolerance by facilitating venous return and cardiac output during an orthostatic challenge. While beneficial in terms of OI, the increase in stiffness, however, may pose cardiovascular health risks if vascular stiffness remains chronically elevated. The identification of the mechanisms responsible for the increase in stiffness provides potential targets for OI countermeasure development or therapeutic intervention depending on whether the change in stiffness is, overall, determined to be beneficial or detrimental. Lastly, the inability of female subjects to increase arterial stiffness during microgravity exposure explains, in part, the increased incidence of OI in females.