title: Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano.
abstract: OBJECTIVE
  To study the nitric oxide (NO) and carbon monoxide roles in the regulation of the pulmonary circulation in lowland and highland newborn sheep and llamas.
  
  
  RESULTS
  We used neonatal sheep (Ovis aries) and llamas (Lama glama) whose gestation and delivery took place at low (580 m) or high (3600 m) altitude. In vivo, we measured the cardiopulmonary function basally and with a NO synthase (NOS) blockade and calculated the production of carbon monoxide by the lung. In vitro, we determined NOS and soluble guanylate cyclase (sGC) expression, NOS activity, and haemoxygenase (HO) expression in the lung. Pulmonary arterial pressure was elevated at high altitude in sheep but not in llamas. Sheep at high altitude relative to sea level had significantly greater total lung NOS activity and eNOS protein, but reduced sGC and HO expression and carbon monoxide production. In contrast, llamas showed no difference in NO function between altitudes, but a pronounced increase in pulmonary carbon monoxide production and HO expression at high altitude.
  
  
  CONCLUSIONS
  In the llama, enhanced pulmonary carbon monoxide, rather than NO, protects against pulmonary hypertension in the newborn period at high altitude. This shift in pulmonary dilator strategy from NO to carbon monoxide has not been previously described, and it may give insight into new treatments for excessive pulmonary vasoconstriction.
authors.affiliation: Programa de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.forename: Roberto V
authors.initials: RV
authors.lastname: Reyes
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Riquelme
authors.forename: Emilia M
authors.initials: EM
authors.lastname: Sanhueza
authors.forename: Germán
authors.initials: G
authors.lastname: Ebensperger
authors.forename: Paola
authors.initials: P
authors.lastname: Casanello
authors.forename: Natalia
authors.initials: N
authors.lastname: Méndez
authors.forename: Renato
authors.initials: R
authors.lastname: Ebensperger
authors.forename: Esteban
authors.initials: E
authors.lastname: Sepúlveda-Kattan
authors.forename: Victor M
authors.initials: VM
authors.lastname: Pulgar
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Cabello
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Blanco
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Julian T
authors.initials: JT
authors.lastname: Parer
authors.forename: Aníbal J
authors.initials: AJ
authors.lastname: Llanos
mesh_terms: D000531:Altitude; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D002161:Camelids, New World / Q000502:physiology*; D002248:Carbon Monoxide / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery / Q000502:physiology*; D012756:Sheep; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D010100:Oxygen