Acute reductions in haematocrit increase flow‐mediated dilatation independent of resting nitric oxide bioavailability in humans
Bibliographic record
Abstract
Key points Changes in haematocrit influence nitric oxide signalling through alterations in shear stress stimuli and haemoglobin scavenging of nitric oxide; these two regulatory factors have not been assessed simultaneously Isovolumic haemodilution led to a marked increase in brachial artery flow‐mediated dilatation in humans The increase in flow‐mediated dilatation occurred in the face of an unaltered shear stress stimulus for vasodilatation and reduced resting steady‐state nitric oxide levels in the blood Collectively, our data point towards haemoglobin scavenging of nitric oxide as a key regulatory factor of brachial flow‐mediated dilatation and highlight the importance of the simultaneous consideration of nitric oxide production and inactivation when investigating vascular function in humans Abstract Haemoglobin (Hb) may impact the transduction of endothelium‐dependent and nitric oxide (NO)‐mediated vasodilator activity, given its contribution to shear stress stimuli and diverse biochemical reactions with NO. We hypothesized that an acute reduction in [Hb] and haematocrit (Hct) would increase brachial artery flow‐mediated dilatation (FMD). In 11 healthy males (28 ± 7 years; 23 ± 2 kg m−2), FMD (Duplex ultrasound), arterial blood gases, Hct and [Hb], blood viscosity, and NO metabolites (ozone‐based chemiluminescence) were measured before and after isovolumic haemodilution, where ∼20% of whole blood was removed and replaced with 5% human serum albumin. Haemodilution reduced Hct by 18 ± 2% (P < 0.001) and whole blood viscosity by 22 ± 5% (P < 0.001). Plasma nitrite (P = 0.01), S‐nitrosothiols (P = 0.03) and total red blood cell NO (P = 0.001) were collectively reduced by ∼15–40%. Brachial artery FMD increased by ∼160% from 3.8 ± 2.1 to 9.7 ± 4.5% (P = 0.004). Statistical covariation for the shear stress stimulus did not alter FMD, indicating that the increase in FMD was not directly related to alterations in whole blood viscosity and the shear stimulus. Collectively, these findings indicate that haemoglobin scavenging of NO appears to be an important factor in the regulation of FMD under normal conditions through constraint of endothelium‐dependent NO‐mediated vasodilatation in healthy humans.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".