Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano.
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.
Herrera
Emilio A
EA
Programa de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Reyes
Roberto V
RV
Giussani
Dino A
DA
Riquelme
Raquel A
RA
Sanhueza
Emilia M
EM
Ebensperger
Germán
G
Casanello
Paola
P
Méndez
Natalia
N
Ebensperger
Renato
R
Sepúlveda-Kattan
Esteban
E
Pulgar
Victor M
VM
Cabello
Gertrudis
G
Blanco
Carlos E
CE
Hanson
Mark A
MA
Parer
Julian T
JT
Llanos
Aníbal J
AJ
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
D009569:Nitric Oxide; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D010100:Oxygen