Endothelium‐dependent vasorelaxation and blood pressure are preserved in mice with chronic hyperendothelinemia
Bibliographic record
Abstract
Endothelin‐1 (ET‐1) is a potent vasoactive peptide implicated in the development of glucose intolerance, endothelial dysfunction, and hypertension. However, whether the detrimental metabolic and vascular effects caused by chronically elevated circulating ET‐1 (i.e., hyperendothelinemia) are exacerbated by obesity remains unknown. Accordingly, six‐week‐old female transgenic mice overexpressing human preproET‐1 selectively in the endothelium (eET‐ 1) and non‐transgenic (i.e., wild‐type) littermates were fed either chow or a Western diet (46% Kcal fat, 36% Kcal carbohydrate) to induce obesity for 21 weeks, creating four distinct groups (n=9–11/group): wild‐type chow‐fed, eET‐1 chow‐fed, wild‐type Western diet‐fed, eET‐1 Western diet‐fed. eET‐1 mice exhibited a 27‐fold (chow) and 18‐fold (Western diet) elevation in plasma ET‐1 concentration relative to wild‐type mice. Notably, despite such marked elevations in plasma ET‐1, blood pressure (systolic and diastolic) and aortic stiffness, assessed by pulse wave velocity, were unaltered in eET‐1 mice relative to wild‐type counterparts, regardless of diet. Similarly, independent of diet, ex vivo endothelium‐dependent relaxation (i.e., vasomotor responses to acetylcholine and insulin) in femoral and coronary arteries were not different between eET‐1 and wild‐type mice, and modestly enhanced in the aorta of eET‐1 mice. eET‐1 mice also exhibited suppressed phenylephrine‐induced aortic vasoconstriction relative to wild‐type mice, an effect that was amplified by Western diet‐feeding. Chow‐fed eET‐1 mice exhibited mild glucose intolerance and this genotype effect was not aggravated by diet‐induced obesity. Collectively, contrary to our hypothesis, we find that endothelial overexpression of ET‐1 does not lead to impaired endothelial function in lean or obese mice. The retention of a functional endothelial phenotype and suppression of alpha‐adrenergic vasoconstriction in this model of chronic hyperendothelinemia may contribute to the preservation of normal blood pressure. Follow‐up experiments are ongoing to delineate potential homeostatic compensatory adaptations that underlie this largely conserved cardiometabolic phenotype in the presence of chronic hyperendothelinemia. Support or Funding Information NIH, SCAN This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".