title: Bosentan decreases pulmonary vascular resistance and improves exercise capacity in acute hypoxia.
abstract: BACKGROUND
  Altitude exposure is associated with mild pulmonary hypertension and decreased exercise capacity. We tested the hypothesis that pulmonary vascular resistance (PVR) contributes to decreased exercise capacity in hypoxic healthy subjects.
  
  
  METHODS
  An incremental cycle ergometer cardiopulmonary exercise test and echocardiographic estimation of pulmonary artery pressure (Ppa) and cardiac output to calculate total PVR were performed in 11 healthy volunteers in normoxia and after 1 h of hypoxic breathing (12% O(2)). The measurements were performed in a random order at 1-week intervals after the receiving either a placebo or bosentan, following a double-blind randomized crossover design. Bosentan was administered twice a day for 3 days, 62.5 mg on the first day and 125 mg on the next 2 days.
  
  
  RESULTS
  Hypoxic breathing decreased the mean (+/- SE) pulse oximetric saturation (Spo(2)) from 99 +/- 1% to 3 +/- 1% and increased the mean PVR from 5.6 +/- 0.3 to 7.2 +/- 0.5 mm Hg/L/min/m(2), together with a decrease in mean maximum O(2) uptake (Vo(2)max) from 47 +/- 2 to 35 +/- 2 mL/kg/min. Bosentan had no effect on normoxic measurements and did not affect hypoxic Spo(2), but decreased PVR to 5.6 +/- 0.3 mm Hg/L/min/m(2) (p < 0.01) and increased Vo(2)max to 39 +/- 2 mL/kg/min (p < 0.01) in hypoxia. Bosentan therapy, on average, restored 30% of the hypoxia-induced decrease in Vo(2)max. Bosentan-induced changes in Ppa and Vo(2)max were correlated (p = 0.01).
  
  
  CONCLUSIONS
  We conclude that hypoxic pulmonary hypertension partially limits exercise capacity in healthy subjects, and that bosentan therapy can prevent it.
authors.affiliation: Department of Physiology, Faculty of Medicine, Free University of Brussels, Belgium.
authors.forename: Vitalie
authors.initials: V
authors.lastname: Faoro
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Boldingh
authors.affiliation: Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Mickael
authors.initials: M
authors.lastname: Moreels
authors.affiliation: Department of Physiology, Faculty of Medicine, Free University of Brussels, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Lamotte
authors.affiliation: Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Unger
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Brussels, Belgium.
authors.forename: Serge
authors.initials: S
authors.lastname: Brimioulle
authors.affiliation: Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Huez
authors.affiliation: Department of Physiology, Faculty of Medicine, Free University of Brussels, Belgium. Electronic address: rnaeije@ulb.ac.be.
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000077300:Bosentan; D002302:Cardiac Output; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan