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

An exaggerated hypoxic pulmonary vasoconstriction is essential for developm ent of high-altitude pulmonary edema (HAPE). We hypothesized that susceptib ility ttl HAPE may be related to decreased production of nitric oxide (NO), an endogenous modulator of pulmonary vascular resistance, and that a decre ase in exhaled NO could be detected during hypoxic exposure. Therefore, we investigated respiratory tract NO excretion by chemiluminescence and pulmon ary artery systolic pressure (Ppa,s) by echocardiography in nine HAPE-susce ptible mountaineers and nine HAPE-resistant control subjects during normoxi a and acute hypoxia (fraction of inspired oxygen [Fi(O2)] = 0.12). The subj ects performed oral breathing. Nasally excreted NO was separated from respi ratory gas by suction via a nasal mask, in HAPE-susceptible subjects, NO ex cretion 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 unch anged (31 +/- 6 versus 33 +/- 6 nl/ min, NS). Nasal NO excretion did not di ffer significantly between groups during normoxia (HAPE-susceptible group, 183 +/- 16 nl/ min; control subjects, 297 +/- 55 nl/min, NS) and was not in fluenced by hypoxia. The changes in Ppa,s with hypoxia correlated with the percent changes in Tower respiratory tract NO excretion (R = -0.49, p = 0.0 4). Our data provide the first evidence of decreased pulmonary NO productio n in HAPE-susceptible subjects during acute hypoxia that may contribute amo ng other factors to their enhanced hypoxic pulmonary vascular response.