Bosentan prevents hypoxia-reoxygenation-induced pulmonary hypertension and improves pulmonary function

Ann Thorac Surg. 1999 Nov;68(5):1714-21; discussion 1721-2. doi: 10.1016/s0003-4975(99)00988-1.


Background: Acute hypoxia results in increased pulmonary vascular resistance. Despite reoxygenation, pulmonary vascular resistance remains elevated and pulmonary function is altered. Endothelin-1 might contribute to hypoxia-reoxygenation-induced pulmonary hypertension and to reoxygenation injury by stimulating leukocytes. This study was carried out using an established model of hypoxia and reoxygenation to determine whether endothelin-1 blockade with Bosentan could prevent hypoxia-reoxygenation-induced pulmonary hypertension and reoxygenation injury.

Methods: Twenty neonatal piglets underwent 90 minutes of hypoxia, 60 minutes of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery. Control animals (n = 12) received no drug treatment, whereas the treatment group (n = 8) received the endothelin-1 receptor antagonist, Bosentan, throughout hypoxia.

Results: In controls, pulmonary vascular resistance increased during hypoxia to 491% of baseline and remained elevated after reoxygenation; however in the Bosentan group, it increased to only 160% of baseline by end-hypoxia, then decreased to 76% at end-recovery. Arterial endothelin-1 levels in controls increased to 591% of baseline after reoxygenation. Arterial nitrite levels decreased during hypoxia in controls but were maintained in the Bosentan group. Consequently, animals in the Bosentan group had better postreoxygenation pulmonary vascular resistance, A-a gradient, and airway resistance along with lower myeloperoxidase levels than controls.

Conclusions: Acute hypoxia and postreoxygenation pulmonary hypertension was attenuated by Bosentan, which maintained nitric oxide levels during hypoxia, decreased leukocyte-mediated injury, and improved pulmonary function.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antihypertensive Agents / pharmacology*
  • Bosentan
  • Cardiopulmonary Bypass
  • Endothelin Receptor Antagonists
  • Endothelin-1 / physiology
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / physiopathology*
  • Nitric Oxide / physiology
  • Oxygen / blood*
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiopathology
  • Receptor, Endothelin A
  • Receptors, Endothelin / physiology
  • Sulfonamides / pharmacology*
  • Swine
  • Vascular Resistance / drug effects*
  • Vascular Resistance / physiology


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • Sulfonamides
  • Nitric Oxide
  • Bosentan
  • Oxygen