title: Inhalation of 35% CO(2) results in activation of the HPA axis in healthy volunteers.
abstract: BACKGROUND
  The hypothalamo-pituitary-adrenal (HPA) axis is a major stress responsive system in humans. Although there are numerous ways of testing responsiveness of the HPA in experimental animals, this is much more difficult in man. Hypercapnea is a very stressful stimulus for humans and has been used as an anxiogenic probe in psychiatric patients. We have now investigated whether the simple challenge of a single 35% inhalation of CO(2) activates the neuroendocrine system as evidenced by changes in HPA activity, as well as cardiovascular and subjective responses, in healthy volunteers.
  
  
  METHODS
  Fourteen healthy male volunteers were recruited. They underwent single vital capacity inhalation of room air and 35% CO(2), in a single blind fashion. Neuroendocrine, cardiovascular and subjective fear measures were taken at regular intervals.
  
  
  RESULTS
  CO(2) inhalation produced significant activation of the HPA axis in all subjects, as measured with plasma cortisol. Heart rate was decreased and systolic blood pressure was significantly increased shortly after the inhalation of CO(2). The subjects reported short-lived symptoms of fear with the experimental gas.
  
  
  CONCLUSIONS
  Single vital capacity inhalation of 35% CO(2) activated the HPA axis in healthy volunteers. It also had a significant cardiovascular and psychological (anxiogenic) effect, as expected from previous published studies. The test is potentially useful in studying the responsivity of the HPA axis in health and disease.
authors.affiliation: Psychopharmacology Unit, School of Medical Sciences, University of Bristol, University Walk, UK.
authors.forename: Spilios V
authors.initials: SV
authors.lastname: Argyropoulos
authors.forename: Jayne E
authors.initials: JE
authors.lastname: Bailey
authors.forename: Sean D
authors.initials: SD
authors.lastname: Hood
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Kendrick
authors.forename: Ann S
authors.initials: AS
authors.lastname: Rich
authors.forename: Gabriel
authors.initials: G
authors.lastname: Laszlo
authors.forename: Jon R
authors.initials: JR
authors.lastname: Nash
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000280:Administration, Inhalation; D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000008:administration & dosage*; D005239:Fear; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016584:Panic Disorder; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D010919:Placebos
chemical_list: D010919:Placebos; D002245:Carbon Dioxide; D006854:Hydrocortisone