title: Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight.
abstract: Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only approximately 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 beta(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 alpha(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.
authors.affiliation: Human Adaptation and Countermeasures Office, Space and Life Sciences Directorate, National Aeronautics and Space Administrattion Johnson Space Center, Houston, TX 77058, USA. jmeck@ems.jsc.nasa.gov
authors.forename: Janice V
authors.initials: JV
authors.lastname: Meck
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Waters
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ziegler
authors.forename: Heidi F
authors.initials: HF
authors.lastname: deBlock
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mills
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Paul L
authors.initials: PL
authors.lastname: Huang
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D001127:Arginine Vasopressin / Q000097:blood; D001341:Autonomic Nervous System / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001810:Blood Volume / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism; D005260:Female; D006400:Hematocrit; D006801:Humans; D007024:Hypotension, Orthostatic / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D013026:Space Flight; D016683:Supine Position / Q000502:physiology; D013575:Syncope / Q000503:physiopathology / Q000517:prevention & control; D014439:Tyramine / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology; D014893:Weightlessness / Q000009:adverse effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D053379:Chromogranin A; D002864:Chromogranins; D016232:Endothelins; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D001127:Arginine Vasopressin; D010656:Phenylephrine; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D014439:Tyramine