Adrenergic control of skeletal muscle blood flow during chronic hypoxia in healthy males
Bibliographic record
Abstract
Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during 1) incremental intra-arterial infusion of phenylephrine to assess α 1 -adrenergic receptor responsiveness and 2) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: −34 ± 15%, vs. HA; +3 ± 18%; P < 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: −45 ± 18% vs. HA: −28 ± 11%; P = 0.009) and high (ΔFVC: SL: −47 ± 20%, vs. HA: −35 ± 20%; P = 0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC ( P = 0.500) and combined α-β-blockade induced a similar vasodilatory response at SL and HA ( P = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA ( P = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-β-blockade at SL (ΔFVC: Control: −27 ± 128 vs. α-β-blockade: +19 ± 23%; P = 0.0004), but unaffected at HA (ΔFVC: Control: −20 ± 22 vs. α-β-blockade: −23 ± 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α 1 -adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.
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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) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".