title: Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema.
abstract: BACKGROUND
  High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung.
  
  
  OBJECTIVE
  We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature.
  
  
  METHODS
  During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects.
  
  
  RESULTS
  Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02).
  
  
  CONCLUSIONS
  Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.
authors.affiliation: Department of Internal Medicine VI (Clinical Pharmacology and Pharmacoepidemiology), University of Heidelberg, Germany.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Berger
authors.forename: Christiane
authors.initials: C
authors.lastname: Hesse
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehnert
authors.forename: Heike
authors.initials: H
authors.lastname: Siedler
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Hubert J
authors.initials: HJ
authors.lastname: Bardenheuer
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Peter
authors.initials: P
authors.lastname: Bärtsch
authors.forename: Walter E
authors.initials: WE
authors.lastname: Haefeli
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000532:Altitude Sickness / Q000209:etiology*; D001794:Blood Pressure; D004198:Disease Susceptibility; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D011654:Pulmonary Edema / Q000209:etiology*; D011659:Pulmonary Gas Exchange; D012039:Regional Blood Flow; D016037:Single-Blind Method; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine