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1-adrenergic Receptor Responses Before Flight and Central Autonomic Dysregulation Post-flight
1 Human Adaptation and Countermeasures Office, Space and Life Sciences Directorate, NASA Johnson Space Center, Houston, TX, USA
2 National Space Biomedical Research Institute, Baylor College of Medicine, Houston, TX, USA
3 Department of Medicine, University of California, San Diego, San Diego, CA, USA
4 Department of Surgery, Albany Medical College, Albany, NY, USA
5 Department of Medicine and Pharmacology, Vanderbilt University, Vanderbilt, TN, USA
6 Department of Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: jmeck{at}ems.jsc.nasa.gov.
Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only about 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and non-presyncopal groups. We studied 22 astronauts ten days before launch, on landing day, and three days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A (a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of norepinephrine); and lymphocyte 
2-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete ten minutes of upright tilt on landing day. When compared to astronauts who were not presyncopal on landing day, presyncopal astronauts had: significantly smaller pressor responses to phenylephrine, both before and after flight; significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; significantly greater norepinephrine release with tyramine on landing day; significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low 
1-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired.
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