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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| 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".