Inorganic nitrate attenuates cardiac dysfunction: roles for xanthine oxidoreductase and nitric oxide
Bibliographic record
Abstract
Background and purpose NO is a vasodilator and independent modulator of cardiac remodelling. Commonly, in cardiac disease (e.g., heart failure), endothelial dysfunction (synonymous with NO deficiency) has been implicated in increased BP, cardiac hypertrophy and fibrosis. Currently, no effective therapies replacing NO have succeeded in the clinic. Inorganic nitrate (NO3−), through chemical reduction to nitrite and then to NO, exerts potent BP lowering, but whether it might be useful in treating undesirable cardiac remodelling is not known. Experimental approach We analysed demographics in a nested age‐ and sex‐matched case–control study of hypertensive patients with or without left ventricular hypertrophy (NCT03088514) and assessed the effects of dietary nitrate in mouse models of cardiac dysfunction. Key results Lower plasma nitrite concentrations and vascular dysfunction accompanied cardiac hypertrophy and fibrosis in patients. In mouse models of cardiac remodelling, restoration of circulating nitrite levels using dietary nitrate improved endothelial dysfunction through targeting the xanthine oxidoreductase‐driven increase in levels of H2O2 and superoxide, and decreased cardiac fibrosis through NO‐mediated block of SMAD phosphorylation leading to improvements in cardiac structure and function. Conclusions and implications Dietary nitrate offers easily translatable therapeutic options for delivery of NO and thereby treatment of cardiac dysfunction.
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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 | 0.000 |
| 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) | 0.002 | 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".