Abstract
To compare the role of nitric oxide in an adaptive process to chronic hypoxia, we examined the effects of endogenous nitric oxide synthase inhibition on pulmonary vascular tone in conscious sheep and pigs living at high altitude. Unanesthetized male sheep (n=6) and pigs (n=5), born and residing in the highlands of Qinghai Province, China (2,300–3,000 m a.s.l.) were studied at that altitude. Pulmonary artery pressure (Ppa), pulmonary artery wedge pressure (Pcwp), and cardiac output (CO) were measured. Pulmonary vascular resistance (PVR) was calculated as (Ppa—Pcwp)/CO. Using a climatic chamber, hemodynamic measurements during exposures to atmospheric pressures corresponding to altitudes of 0, 2,300, and 4,500 m a.s.l. were performed with and without NO inhibition, using Nw-nitro-l-argine (NLA; 20 mg kg−1), a potent stereospecific competitive inhibitor of nitric oxide synthase. Ppa and PVR at baseline (2,300 m) and during hypoxic exposure (4,500 m) were significantly higher in pigs than in sheep. After NLA administration, Ppa increased and CO decreased in both animals, resulting in significantly increased PVR at baseline and during hypoxic exposure. However, there were no significant differences in the percent increase in basal or hypoxic PVR after NLA administration between sheep and pigs. We conclude that augmented endogenous NO production could contribute to the regulation of pulmonary vascular tone at high altitude in sheep and pigs. However, it is unlikely that NO is responsible for the different pulmonary vascular tones between sheep and pigs at basal condition at moderately high altitude.
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Abbreviations
- CO :
-
cardiac output
- HPV :
-
hypoxic pulmonary vasoconstriction
- NLA :
-
Nw-nitro-l-argine
- NO :
-
nitric oxide
- NOS :
-
nitric oxide synthase
- P cwp :
-
pulmonary artery wedge pressure
- P pa :
-
pulmonary artery pressure
- P sa :
-
systemic artery pressure
- PVR :
-
pulmonary vascular resistance
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Acknowledgements
This work was supported by a Grant of the Japanese Ministry of Science and Sports (no. 12576001). We thank the staff at the Qinghai High Altitude Medical Science Institute, Xining, China for assistance.
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Ruan, Z., Koizumi, T., Sakai, A. et al. Comparison of pulmonary vascular response to endogenous nitric oxide inhibition in sheep and pigs living at 2,300 m. J Comp Physiol B 174, 549–554 (2004). https://doi.org/10.1007/s00360-004-0443-3
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DOI: https://doi.org/10.1007/s00360-004-0443-3