title: Bosentan prevents hypoxia-reoxygenation-induced pulmonary hypertension and improves pulmonary function.
abstract: 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.
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. pearj0@chmcc.org
authors.forename: J M
authors.initials: JM
authors.lastname: Pearl
authors.forename: S A
authors.initials: SA
authors.lastname: Wellmann
authors.forename: J L
authors.initials: JL
authors.lastname: McNamara
authors.forename: J P
authors.initials: JP
authors.lastname: Lombardi
authors.forename: C J
authors.initials: CJ
authors.lastname: Wagner
authors.forename: J L
authors.initials: JL
authors.lastname: Raake
authors.forename: D P
authors.initials: DP
authors.lastname: Nelson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000077300:Bosentan; D002315:Cardiopulmonary Bypass; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000097:blood*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D013449:Sulfonamides; D009569:Nitric Oxide; D000077300:Bosentan; D010100:Oxygen