Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema

Am J Respir Crit Care Med. 2001 Feb;163(2):368-73. doi: 10.1164/ajrccm.163.2.2001134.


An exaggerated hypoxic pulmonary vasoconstriction is essential for development of high-altitude pulmonary edema (HAPE). We hypothesized that susceptibility to HAPE may be related to decreased production of nitric oxide (NO), an endogenous modulator of pulmonary vascular resistance, and that a decrease in exhaled NO could be detected during hypoxic exposure. Therefore, we investigated respiratory tract NO excretion by chemiluminescence and pulmonary artery systolic pressure (Ppa,s) by echocardiography in nine HAPE-susceptible mountaineers and nine HAPE-resistant control subjects during normoxia and acute hypoxia (fraction of inspired oxygen [FI(O2)] = 0.12). The subjects performed oral breathing. Nasally excreted NO was separated from respiratory gas by suction via a nasal mask. In HAPE-susceptible subjects, NO excretion in expired gas significantly decreased (p < 0.05) during hypoxia of 2 h in comparison with normoxia (28 +/- 4 versus 21 +/- 2 nl/min, mean +/- SEM). In contrast, the NO excretion rate of control subjects remained unchanged (31 +/- 6 versus 33 +/- 6 nl/ min, NS). Nasal NO excretion did not differ significantly between groups during normoxia (HAPE-susceptible group, 183 +/- 16 nl/ min; control subjects, 297 +/- 55 nl/min, NS) and was not influenced by hypoxia. The changes in Ppa,s with hypoxia correlated with the percent changes in lower respiratory tract NO excretion (R = -0.49, p = 0.04). Our data provide the first evidence of decreased pulmonary NO production in HAPE-susceptible subjects during acute hypoxia that may contribute among other factors to their enhanced hypoxic pulmonary vascular response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Altitude Sickness / physiopathology*
  • Breath Tests*
  • Humans
  • Hypoxia / physiopathology*
  • Lung / blood supply
  • Male
  • Middle Aged
  • Nitric Oxide / physiology*
  • Pulmonary Edema / physiopathology*
  • Pulmonary Gas Exchange / physiology
  • Vasoconstriction / physiology


  • Nitric Oxide