The Role of NADPH Oxidase in Regulating Cerebral Vascular Myogenic Tone
Bibliographic record
Abstract
The myogenic response refers to the intrinsic ability of arteries to constrict to elevated pressure. The underlying mechanism has yet to be elucidated but recent evidence suggests that the angiotensin II type 1 receptor (AT1R) is a key mechanosensor, linking intravascular pressure to tone development. One intriguing aspect of this receptor is its ability to activate NADPH oxidase (Nox), an enzyme responsible for the production of reactive oxygen species. The goal of this study was to ascertain the role of Nox in myogenic tone development. Briefly, rat cerebral arteries were mounted in a myograph, pressurized to 60mmHg and diameter monitored prior to and following the application of apocynin (a general Nox inhibitor) or ML171 (a Nox1 specific inhibitor). Myogenic constriction progressively rose as vessels were pressurized from 20 to 60 mmHg. These pressure‐induced responses were attenuated by apocynin in a concentration dependent manner (37% vs 24% at 60 mmHg) irrespective of whether the endothelium was present or absent. ML171 (30μM) was equally effective at moderating the myogenic response (36% vs 24%); control experiments showed no discernible role for Nox2. Similar attenuating effects were observed in human cerebral arteries. These findings indicate Nox1 is expressed in rat cerebral arterial smooth muscle and may be a regulator of pressure‐induced responses. While the precise downstream mechanism has yet to be resolved, the L‐type Ca 2+ channel is a likely target of Nox regulation. This work sheds new light on mechanosensation and how unique signaling proteins impact the ability of resistance arteries to respond to intravascular pressure. Support or Funding Information This work is supported by an operating grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) for DG Welsh. DG Welsh is a Rorabeck chair in molecular neuroscience and vascular biology at the University of Western Ontario. AM Hashad is a Vanier scholar (CIHR) and was supported by a salary studentship from Alberta Innovates Health solutions (AIHS).
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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 | 0.000 |
| 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".