The Functional Contribution Of Myoendothelial Feedback To Arterial Tone Is Determined By The Nature Of The Vasoconstricion
Bibliographic record
Abstract
Constriction of resistance arteries in response to global application of agonists is modulated by activation of the endothelium via myoendothelial feedback. Recent evidence supports a model of myoendothelial feedback in which generation of localized InsP 3 ‐dependent Ca 2+ transients leads to activation of intermediate conductance Ca 2+ ‐activated K + (IK Ca ) channels to hyperpolarize the endothelium. We have now investigated the functional contribution of this pathway to limiting responses to two physiologically important vasoconstrictor stimuli, activation of sympathetic nerves and increases in intravascular pressure. In isolated segments of rat mesenteric resistance artery mounted in a wire or pressure myograph, pharmacological inhibition of IK Ca channels significantly potentiated increases in tone elicited by global application agonists such as noradrenaline, but did not significantly alter increases in tone elicited by stimulation of sympathetic perivascular nerves, or myogenic reactivity elicited by step‐wise increases in intravascular pressure. Similarly, in the endothelium‐intact perfused mesenteric bed, blockers of IK Ca channels enhanced vasoconstriction to exogenous noradrenaline but had no effect on nerve‐evoked vasoconstriction. However, the influence of the endothelium on responses to sympathetic nerve stimulation was inhibited by blockers of nitric oxide signaling and by inhibition of small conductance Ca 2+ ‐activated K + (SK Ca ) channels. These data demonstrate that the contribution of myoendothelial feedback to endothelium‐dependent modulation of tone is determined by the stimulus for smooth muscle contraction. Although activated by global application of contractile agonists, the myoendothelial feedback pathway does not appear to play a significant role in modulating myogenic reactivity or nerve‐evoked responses in resistance arteries. Furthermore, in the intact mesenteric vascular bed, under conditions of constant flow, increases in shear stress rather than myoendothelial feedback, may be the predominant stimulus for engagement of the endothelium to oppose nerve‐evoked vasoconstriction. Support or Funding Information Supported by a grant‐in‐aid from the Heart and Stroke Foundation of Alberta, Nunavut and the North West Territories to FP (G130003076)
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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 | 0.000 |
| 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".