Acute hypoxaemia and vascular function in healthy humans

Endothelium-dependent flow mediated dilation (FMD) and endothelium-independent dilation (GTN) are impaired at high altitude (5050 m), and FMD is impaired following acute exposure (<60-minutes) to normobaric hypoxia equivalent to ∼5050 m (∼FI O2  = 0.11). Whether glyceryl trinitrate (GTN)-induced dilation is impaired acutely, and whether FMD is impaired during milder hypoxia is unknown. Therefore, we assessed brachial FMD at baseline and following 30-minutes of mild (74 ± 2 mmHg PET O₂) and moderate (50 ± 3 mmHg PET O₂) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-dilaiton following the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared to normoxic baseline, reduction during mild and moderate hypoxic exposure were evident in FMD (mild vs moderate: -1.2 ± 1.1% vs. -3.1 ± 1.7%; P = 0.01) and GTN-dilation (-2.1 ± 1.0 vs. -4.2 ± 2.0; P = 0.01); the decline in FMD and GTN-dilation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve (SRAUC ), relative FMD was attenuated in both conditions (mild vs moderate: 0.6 ± 0.9% vs. 0.8 ± 0.7%; P ≤ 0.01). Following 30-minutes of normoxic time-control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental declines in smooth muscle vasodilator capacity (impaired GTN-dilation). Our findings from the normoxic controls study, suggest the decline in FMD in acute hypoxia also appears to be influenced by 30-minutes of supine rest/inactivity. This article is protected by copyright. All rights reserved.