title: Recombinant angiotensin-converting enzyme 2 suppresses pulmonary vasoconstriction in acute hypoxia.
abstract: OBJECTIVE
  Alveolar hypoxia as a result of high altitude leads to increased pulmonary arterial pressure. The renin-angiotensin system is involved in the regulation of pulmonary arterial pressure through angiotensin-converting enzyme 2 (ACE2). It remains unknown whether ACE2 administration alters pulmonary vascular pressure in hypoxia.
  
  
  METHODS
  We investigated 12 anesthetized pigs instrumented with arterial, central venous, and Swan-Ganz catheters exposed to normobaric hypoxia (fraction of inspired oxygen = 0.125) for 180 minutes. After taking baseline measurements in normoxia and hypoxia, ACE2 400 μg·kg(-1) was administered to 6 animals, and another 6 served as control. Ventilatory variables, arterial blood gases, ventilation/perfusion (V̇A/Q̇) relationships, and plasma angiotensin II concentrations were assessed before and at 30, 90, and 150 minutes in hypoxia after ACE2 or placebo administration. Hemodynamic variables and cardiac output were observed every 30 minutes.
  
  
  RESULTS
  We observed lower pulmonary arterial pressure (maximum: 30 vs 39 mm Hg, P < .01) and lower pulmonary vascular resistance (maximum: 4.1 vs 7.5 Wood units, P <.01) in animals treated with ACE2. There was a trend (P =.09) toward lower angiotensin II plasma concentrations among ACE2-treated animals. Cardiac variables and systemic arterial pressure in hypoxia remained unaffected by ACE2. Ventilation/perfusion relationships and Pao(2) did not differ between groups.
  
  
  CONCLUSIONS
  In acute pulmonary hypertension, administration of ACE2 blunts the rise in pulmonary arterial pressure that occurs in response to hypoxia. Recombinant ACE2 may be a treatment option for high altitude pulmonary edema and hypoxia-associated pulmonary hypertension.
authors.affiliation: Section of Respiratory and Altitude Research, Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria. axel.kleinsasser@i-med.ac.at
authors.forename: Axel
authors.initials: A
authors.lastname: Kleinsasser
authors.forename: Iris
authors.initials: I
authors.lastname: Pircher
authors.forename: Benedict
authors.initials: B
authors.lastname: Treml
authors.forename: Martin
authors.initials: M
authors.lastname: Schwienbacher
authors.forename: Manfred
authors.initials: M
authors.lastname: Schuster
authors.forename: Eveline
authors.initials: E
authors.lastname: Janzek
authors.forename: Hans
authors.initials: H
authors.lastname: Loibner
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Alex
authors.initials: A
authors.lastname: Loeckinger
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001784:Blood Gas Analysis; D005260:Female; D006439:Hemodynamics; D000860:Hypoxia; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2