Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans

Eur J Clin Invest. 2010 Mar;40(3):195-202. doi: 10.1111/j.1365-2362.2010.02254.x.


Background: Activation of the endothelin-1 (ET-1) pathway may be involved in hypoxia-induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10).

Design: We used a double-blind, placebo-controlled, randomized, cross-over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90-min-exposure to normobaric hypoxia (FiO(2) = 0.12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O(2) saturation (SaO(2)), and blood gases at rest and during a sub-maximal exercise.

Results: PASP in normoxia at rest was 23.5 +/- 2.7 and during exercise 39.8 +/- 11.6 mmHg (P < 0.0001). During the placebo period, hypoxia induced a significant decrease in SaO(2), PaO(2) and PCO(2) and increase in pH. PASP at rest increased significantly: 32.1 +/- 3.5 mmHg (P < 0.001 vs. normoxia). Bosentan significantly blunted the hypoxia-induced increase in PASP: bosentan: 27.0 +/- 3.3 mmHg, P = 0.002 vs. placebo at rest, but not during exercise: bosentan 39.8 +/- 11.6 vs. placebo 43.0 +/- 8.5 mmHg, ns. Bosentan had no effect on the hypoxia-induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia.

Conclusion: A single oral dose of bosentan blunted an acute hypoxia-induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure.

Trial registration: ClinicalTrials.gov NCT00026081.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Blood Gas Analysis
  • Blood Pressure / drug effects*
  • Bosentan
  • Cardiac Output / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Echocardiography
  • Endothelin Receptor Antagonists*
  • Exercise / physiology
  • Humans
  • Hypoxia / drug therapy*
  • Hypoxia / physiopathology
  • Male
  • Middle Aged
  • Oxygen / metabolism
  • Pulmonary Artery / drug effects
  • Pulmonary Circulation / drug effects*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Sulfonamides
  • Bosentan
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT00026081