EFFECTS OF EXPOSURE TO HIGH-ALTITUDE ON PLASMA ENDOTHELIN-1 LEVELS INNORMAL SUBJECTS

Objective: To assess whether the hypoxia associated with exposure to h igh altitude affects plasma endothelin-1 levels, and whether changes i n endothelin-1 are related to those in systemic and pulmonary blood pr essure. Design: Eight normal subjects ascended Mount Everest to an alt itude of 5050 m within a period of 8 days (study 1) and 10 ascended Mo unt Rosa in the Italian Alps to an altitude of 4559 m within 2 days (s tudy 2). In study 1 systemic blood pressure, heart rate, haematocrit, haemoglobin oxygen saturation (evaluated by percutaneous oximetry) and venous plasma endothelin-1 were measured several times during the asc ent, and twice more during the time spent at high altitude. In study 2 the same parameters as well as systolic pulmonary pressure by echocar diography were evaluated on the second day of resting at 4559 m. In bo th studies, data obtained during the expeditions were compared with th ose collected from the same subjects at sea level. Results: In study 1 plasma endothelin-1 increased progressively up to 4240 m (from 1.8 +/ - 0.1 pg/ml at sea level to 2.7 +/- 0.2 pg/ml) and decreased slightly thereafter; these increments were directly related to the decrements i n percutaneous oxygen saturation, which, at that altitude, fell from 9 8.6 +/- 0.2% at sea level to 80.8 +/- 0.4%. Blood pressure and haemato crit also rose in response to exposure to high altitude but these chan ges were not related to changes in endothelin-1. In study 2 the increm ents in plasma endothelin-1 were similar to those observed in study 1 and the changes again correlated with changes in oxygen saturation as well as with those in systolic pulmonary pressure. On average, systoli c pulmonary pressure increased from 19 +/- 1 to 26 +/- 1.9 mmHg, where as systemic blood pressure and haematocrit were unchanged. Conclusion: Exposure to high altitude is associated with consistent increases in plasma endothelin-1. This is probably the result of augmented secretio n of the peptide in response to hypoxia and may contribute to the phys ioiogical adaptation of the pulmonary circulation to this condition.