title: Circulatory responses to orthostasis during alpha1-adrenergic receptor blockade at high altitude.
abstract: BACKGROUND
  Increased blood level of norepinephrine, a primary alpha-adrenergic agonist, is associated with high-altitude exposure, and may help regulate key physiological functions (e.g., blood pressure). We hypothesized that blocking alpha1-adrenergic receptors would impair circulatory compensation for an orthostatic challenge to a greater extent at altitude than at sea level.
  
  
  METHODS
  Sixteen healthy women (23 +/- 2 yr) were randomly assigned to receive either 2 mg prazosin (n = 8) or placebo (n = 8) t.i.d. (double-blind design) for 12 d at sea level and during the first 12 d of altitude residence (4300 m). Passive 60 degrees upright tilt was performed at sea level (10 d of treatment), and after 3 and 10 d at altitude. Mean arterial BP (MABP, via auscultation) and heart rate (HR, via ECG) were measured every min during 10 min each of supine rest and tilt.
  
  
  RESULTS
  For the prazosin group compared with the placebo group: 1.) Supine and tilt MABP were consistently lower (p < 0.05) at sea level; 2.) MABP did not differ (p > 0.05) for either day at altitude; 3.) HR was similar for both positions at sea level and altitude; and 4.) MABP was consistently less only at sea level and HR was consistently greater only at altitude (both p < 0.05) in response to tilt.
  
  
  CONCLUSIONS
  alpha1-adrenergic blockade altered MABP and HR responses to tilt at sea level and altitude, but circulatory responses to orthostasis were well maintained in both environments. At altitude, BP during tilt was sufficiently maintained by a compensatory increase in heart rate, likely mediated by parasympathetic withdrawal.
authors.affiliation: Thermal and Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA. charles.fulco@na.amedd.army.mil
authors.forename: C S
authors.initials: CS
authors.lastname: Fulco
authors.forename: P B
authors.initials: PB
authors.lastname: Rock
authors.forename: S R
authors.initials: SR
authors.lastname: Muza
authors.forename: E E
authors.initials: EE
authors.lastname: Wolfel
authors.forename: L G
authors.initials: LG
authors.lastname: Moore
authors.forename: A
authors.initials: A
authors.lastname: Cymerman
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000328:Adult; D000531:Altitude; D001794:Blood Pressure / Q000502:physiology*; D002395:Catecholamines / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D011187:Posture / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D018667:Tilt-Table Test
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002395:Catecholamines; D011224:Prazosin