Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation.
High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed subjects at altitudes above 2,500 m. It is not clear whether, in addition to hemodynamic factors and defective alveolar fluid clearance, inflammation plays a pathogenic role in HAPE. We therefore made serial measurements of exhaled pulmonary nitric oxide (NO), a marker of airway inflammation, in 28 HAPE-prone and 24 control subjects during high-altitude exposure (4,559 m). To examine the relationship between pulmonary NO synthesis and pulmonary vascular tone, we also measured systolic pulmonary artery pressure (Ppa). In the 13 subjects who developed HAPE, exhaled NO did not show any tendency to increase during the development of lung edema. Throughout the entire sojourn at high altitude, pulmonary exhaled NO was roughly 30% lower in HAPE-prone than in control subjects, and there existed an inverse relationship between Ppa and exhaled NO (r = -0.51, p < 0.001). These findings suggest that HAPE is not preceded by airway inflammation. Reduced exhaled NO may be related to altered pulmonary NO synthesis and/or transport and clearance, and the data in our study could be consistent with the novel concept that in HAPE-prone subjects, a defect in pulmonary epithelial NO synthesis may contribute to exaggerated hypoxic pulmonary vasoconstriction and in turn to pulmonary edema.
Duplain
H
H
Department of Internal Medicine and the Botnar Center for Clinical Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Sartori
C
C
Lepori
M
M
Egli
M
M
Allemann
Y
Y
Nicod
P
P
Scherrer
U
U
D000328:Adult; D000531:Altitude; D001794:Blood Pressure; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D011654:Pulmonary Edema / Q000276:immunology* / Q000503:physiopathology*; D012119:Respiration; D013599:Systole
D009569:Nitric Oxide