Role of reactive oxygen species in mediating peripheral hypoxic vasodilation and sympathoexcitation at high altitude
Bibliographic record
Abstract
High-altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) via activation of the arterial chemoreflex, pulmonary arterial baroreceptors and resetting of the sympathetic vascular baroreflex. However attempting to silence these mechanisms only partially normalises MSNA, implicating other contributory mechanisms. Increased oxidant production may modulate central sympathetic outflow, while potentially modifying chemosensitivity and vasomotor signalling to the peripheral and pulmonary vasculature. Therefore we tested the hypothesis that blunting oxidative stress would reduce MSNA at high altitude. MSNA (microneurography of the peroneal nerve), continuous arterial pressure (photoplethysmography), vascular tone (duplex ultrasound of the brachial artery), pulmonary artery systolic pressure (PASP, echocardiography) and carotid body tonic activity (1-min hyperoxia) were measured pre- and post-ascorbic acid infusion (200 mg/min for 15-min and then 40 mg/min) in healthy lowlanders (n = 15) after 3-7 days of high-altitude exposure (3800 m). Ascorbic acid infusion improved the redox environment, determined by an increase in whole cell nuclear factor erythroid 2-related factor 2 activity (P = 0.005). Post-infusion MSNA burst frequency (-2 ± 2 bursts/min, P = 0.007) and incidence (-5 ± 4 bursts/100 heartbeats (HB), P = 0.006) decreased. However the infusion increased mean arterial (9 ± 4 mmHg, P≤0.001), systolic (11 ± 8 mmHg, P ≤ 0.004) and diastolic pressure (7 ± 4 mmHg, P ≤ 0.001) and total peripheral resistance (P = 0.013) concomitantly with a reduction in brachial diameter (-0.12 ± 0.14 mm, P = 0.002). Carotid body tonic activity (P = 0.247) and PASP (P = 0.365) remained unchanged by ascorbic acid infusion. In conclusion improving the antioxidant environment lowered MSNA at high altitude; however the small reduction is likely a consequence of the increased blood pressure secondary to the blunting of hypoxic vasodilation rather than a direct effect on sympathetic outflow. KEY POINTS: High-altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) from sea level values. Pulmonary artery systolic pressure (PASP), peripheral arterial chemoreflex and high altitude-induced hypovolaemia are involved in the increase in MSNA; however current evidence indicates additional contributory mechanisms. Hypoxia associated with high altitude results in an increase in the production of reactive oxygen species (ROS), which may be sympathoexcitatory. Therefore we tested the hypothesis that improving the redox environment using an ascorbic acid infusion would lower sympathetic nerve activity. After the infusion, sympathetic nerve activity was reduced alongside an increase in vascular tone and elevation in blood pressure. The reduction in MSNA occurred independently of changes in PASP and chemoreflex activity. Our findings demonstrate that ROS elevates sympathetic nerve activity at high altitude; however this reduction is likely a result of the elevated blood pressure after the blunting of hypoxic vasodilation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".