Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation
Bibliographic record
Abstract
Key points Information describing alterations in vascular function during either acute or prolonged normobaric or hypobaric hypoxia is sparse and often confounded by pathology and methodological limitations. We show that high altitude exposure in lowlanders is associated with impairments in both endothelial and smooth muscle function, and with increased central arterial stiffness; furthermore, in all of these respects, lowlanders’ vasculature becomes comparable to that of natives born and raised at altitude. Changes in endothelial function occur very rapidly in normobaric hypoxia, and partly under the influence of sympathetic nerve activity. Thus, a lifetime of high‐altitude exposure neither attenuates nor intensifies the impairments in vascular function observed with short‐term exposure in lowlanders; such impairment and altered structure likely translate into an elevated cardiovascular risk. Abstract Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high‐altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium‐dependent flow‐mediated dilatation (FMD), endothelium‐independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical‐mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO 2 – ) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs . 6.8 ± 0.4%; P = 0.004) and GTN‐induced dilatation (16.6 ± 0.9 vs . 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs . 6.6 ± 0.3 m s −1 ; P = 0.001). These changes persisted at days 12–14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO 2 – increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN‐induced dilatation evident during acute ( n = 11, r = −0.53) and chronic ( n = 7, r = −0.69; P ≤ 0.01) exposure to 5050 m. In a follow‐up, placebo‐controlled experiment ( n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspired O 2 fraction ( ) = 0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs . 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α 1 ‐adrenoreceptor blockade. In conclusion, high‐altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high‐altitude exposure neither intensifies nor attenuates the impairments seen with short‐term exposure, chronic high‐altitude exposure appears to be associated with arterial remodelling.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".