Nitric oxide contributes to cerebrovascular shear‐mediated dilatation but not steady‐state cerebrovascular reactivity to carbon dioxide
Bibliographic record
Abstract
Abstract Cerebrovascular CO 2 reactivity (CVR) is often considered a bioassay of cerebrovascular endothelial function. We recently introduced a test of cerebral shear‐mediated dilatation (cSMD) that may better reflect endothelial function. We aimed to determine the nitric oxide (NO)‐dependency of CVR and cSMD. Eleven volunteers underwent a steady‐state CVR test and transient CO 2 test of cSMD during intravenous infusion of the NO synthase inhibitor N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA) or volume‐matched saline (placebo; single‐blinded and counter‐balanced). We measured cerebral blood flow (CBF; duplex ultrasound), intra‐arterial blood pressure and . Paired arterial and jugular venous blood sampling allowed for the determination of trans‐cerebral NO 2 − exchange (ozone‐based chemiluminescence). l ‐NMMA reduced arterial NO 2 − by ∼25% versus saline (74.3 ± 39.9 vs . 98.1 ± 34.2 nM; P = 0.03). The steady‐state CVR (20.1 ± 11.6 nM/min at baseline vs . 3.2 ± 16.7 nM/min at +9 mmHg ; P = 0.017) and transient cSMD tests (3.4 ± 5.9 nM/min at baseline vs . −1.8 ± 8.2 nM/min at 120 s post‐CO 2 ; P = 0.044) shifted trans‐cerebral NO 2 − exchange towards a greater net release (a negative value indicates release). Although this trans‐cerebral NO 2 − release was abolished by l ‐NMMA, CVR did not differ between the saline and l ‐NMMA trials (57.2 ± 14.6 vs . 54.1 ± 12.1 ml/min/mmHg; P = 0.49), nor did l ‐NMMA impact peak internal carotid artery dilatation during the steady‐state CVR test (6.2 ± 4.5 vs . 6.2 ± 5.0% dilatation; P = 0.960). However, l ‐NMMA reduced cSMD by ∼37% compared to saline (2.91 ± 1.38 vs . 4.65 ± 2.50%; P = 0.009). Our findings indicate that NO is not an obligatory regulator of steady‐state CVR. Further, our novel transient CO 2 test of cSMD is largely NO‐dependent and provides an in vivo bioassay of NO‐mediated cerebrovascular function in humans. image Key points Emerging evidence indicates that a transient CO 2 stimulus elicits shear‐mediated dilatation of the internal carotid artery, termed cerebral shear‐mediated dilatation. Whether or not cerebrovascular reactivity to a steady‐state CO 2 stimulus is NO‐dependent remains unclear in humans. During both a steady‐state cerebrovascular reactivity test and a transient CO 2 test of cerebral shear‐mediated dilatation, trans‐cerebral nitrite exchange shifted towards a net release indicating cerebrovascular NO production; this response was not evident following intravenous infusion of the non‐selective NO synthase inhibitor N G ‐monomethyl‐ l ‐arginine. NO synthase blockade did not alter cerebrovascular reactivity in the steady‐state CO 2 test; however, cerebral shear‐mediated dilatation following a transient CO 2 stimulus was reduced by ∼37% following intravenous infusion of N G ‐monomethyl‐ l ‐arginine. NO is not obligatory for cerebrovascular reactivity to CO 2 , but is a key contributor to cerebral shear‐mediated dilatation.
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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 | 0.001 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".