The role of hypoxia related hormones responses in acute mountain sickness susceptibility individuals unaccustomed to high altitude

Acute mountain sickness (AMS) is caused by rapid ascent to altitude (>2500 m) and remains a poorly understood pathophysiological condition. Accordingly, we investigated the relationship between acute exposure to high altitude and hypoxia related biochemical proteins. 21 healthy subjects (Female (8) and male (13), Age: 36.7±8.5, BMI: 23.2±3.1) volunteers participated in this project and fasting blood samples were taken before (sea level) and after 1 and 24-h exposure to high altitude (3,550 m). Blood oxygen saturation (SpO(2)), AMS status (Lake Louise Score) and serum HIF-1, Endothelin-1, VEGF and Orexin-A were measured (via ELISA) at 1, 6 and 24 h after exposure to high altitude. Pre-ascent measurement of hypoxia related proteins (Orexin-A, HIF-1, VEGF and Endothelin-1) where all significantly (<0.05) higher in the AMS-resistant individuals (No-AMS) when compared to AMS susceptible individuals (AMS+). Upon ascent to high altitude, 11 out of 21 volunteers had AMS (10.1±0.6 in AMS+ vs. 0.9±0.6 in No-AMS, P<0.05) and presented with lower resting SpO(2) levels (77.7±0.4 vs. 83.5±0.3 respectively, p<0.05). Orexin-A, HIF-1, VEGF and Endothelin-1, significantly increased 24 hrs after exposure to high altitude in both AMS+ and No-AMS. The response of Orexin-A was similar between two groups, also, HIF-1 elevation 24 hrs after exposure to altitude was more in AMS+ (13% vs. 19%), but the increase of VEGF and Endothelin-1, 1 and 24 hrs after exposure to altitude in No-AMS was double that of AMS+. Hypoxia related proteins include Orexin-A, HIF-1, VEGF and Endothelin-1 may play a pathophysiological role in those who are susceptible to AMS.