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Cardiovascular Research Advance Access originally published online on September 18, 2007
Cardiovascular Research 2008 77(1):197-201; doi:10.1093/cvr/cvm013
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For Permissions please email: journals.permissions@oxfordjournals.org

Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano

Emilio A. Herrera1,2,3,{dagger}, Roberto V. Reyes1,{dagger}, Dino A. Giussani2, Raquel A. Riquelme4, Emilia M. Sanhueza1, Germán Ebensperger1,5, Paola Casanello1,{ddagger}, Natalia Méndez1, Renato Ebensperger1, Esteban Sepúlveda-Kattan1,{ddagger}, Victor M. Pulgar1,¶, Gertrudis Cabello5,6, Carlos E. Blanco7, Mark A. Hanson8, Julian T. Parer9 and Aníbal J. Llanos1,3,5,*

1 Programa de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile
2 Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
3 International Centre for Andean Studies (INCAS), Universidad de Chile, Santiago-Arica, Chile
4 Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
5 Universidad de Tarapacá y Centro de Investigaciones del Hombre en el Desierto, Arica, Chile
6 Facultad de Ciencias, Universidad de Tarapacá, Arica, Chile
7 Department of Pediatrics, University of Maastricht, Maastricht, The Netherlands
8 Centre for Developmental Origins of Health and Disease, University of Southampton, Southampton, UK
9 Department of Obstetrics and Gynecology, University of California San Francisco, CA, USA

* Corresponding author. Av Salvador 486 CP6640871 Tel: +56 2 3419147; fax: +56 2 2741628. E-mail address: allanos{at}med.uchile.cl

Aims: 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.

Methods and 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.

KEYWORDS Hypoxia/anoxia; Pulmonary circulation; Endothelial function; Nitric oxide; Vasoconstriction/dilation

Time for primary review: 17 Days

{dagger} These authors contributed equally.

{ddagger} Present address. Pontificia Universidad Católica de Chile, Santiago, Chile.

Present address. Department of Obstetrics and Gynecology, Wake Forest University, Winston Salem, NC 27157, USA.


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