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1-adrenergic receptor responses before flight and central autonomic dysregulation postflight
1Human Adaptation and Countermeasures Office, Space and Life Sciences Directorate, National Aeronautics and Space Administration Johnson Space Center, Houston, 77058; 2National Space Biomedical Research Institute, Baylor College of Medicine, Houston, Texas 77030; 3Department of Medicine, University of California, San Diego, California 92103; 4Department of Surgery, Albany Medical College, Albany, New York 12208; 5Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee 37232; and 6Department of Cardiology, Massachusetts General Hospital, Boston, Massachusetts 02129
Submitted 4 August 2003 ; accepted in final form 3 December 2003
Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only 
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 nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 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 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1) significantly smaller pressor responses to phenylephrine both before and after flight; 2) significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3) significantly greater norepinephrine release with tyramine on landing day; and 4) 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.
tyramine; phenylephrine; dihydroxyphenylglycol; tilt tests; arginine vasopressin
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