Abstract Mo127: Nitrate Supplementation Plus Voluntary Activity in C57Bl/6 Mice Improves Fitness and Impairs Cardiac Calcium Handling In a Sex Specific Fashion
Bibliographic record
Abstract
Nitrate supplements are commonly combined with aerobic exercise to potentially improve performance and cardiac function. Whether this combination benefits cardiac function at the organ and cellular levels is unclear. We will determine if nitrates affect fitness or cardiac function in both sexes. C57Bl/6 mice (9-mos) were given 1mM sodium nitrate (drinking water) and/or access to a running wheel for 3 mos. Cardiac function (echocardiography), blood pressure (tail cuff) and fitness (treadmill) were measured. Calcium transients (Fura-2) and contractions (2Hz) were measured in ventricular myocytes and calcium handling proteins were measured by qPCR. In both sexes, nitrates did not change blood pressure or voluntary wheel running although females ran more than males (3.7±0.3km vs 2.2±0.3km, p=0.002). In exercised female mice, nitrates increased fitness from baseline while control did not (top speed at exhaustion: 24.2±1.4 to 28.0±1.5 cm/s, p=0.07 vs 23.3±1.0 to 30.7±2.0 cm/s, p=0.002) but nitrate supplemented males showed no fitness benefit. However, while exercise improved cardiac function and contractility compared to sedentary mice, nitrates plus exercise impaired cardiac function in a sex-specific manner. Nitrate-treated males who exercised had lower E/A ratios (1.8±0.3 vs 1.3±0.1, p=0.01) and worse diastolic function than control exercised males. By contrast, nitrate-treated female mice who exercised had smaller global longitudinal strain (-19.5±1.5 vs -11.8±3.0%, p=0.01) than controls, indicative of worse systolic function. Corresponding changes were seen at the cellular level. Exercised males given nitrates had slower a calcium transient decay than controls (44.8±4 vs 73.8±6 ms, p=0.01), while females given nitrates had slower velocity to peak calcium (0.031±0.004 vs 0.018±0.003 µm/ms, p=0.005) and smaller cellular contractions (2.9±0.5 µm vs 1.4±0.5 µm: p=0.03). Cardiac calcium handling proteins were also modified in females. Exercise plus nitrates caused a decrease in SERCA2a and ryanodine receptor 2 expression (mRNA) compared to the control exercise group. Studies in males are ongoing. Exercise plus nitrates increased fitness levels in only females and reduced cardiac function in a sex specific way when compared to exercise alone. This suggests a potential balance between benefits to fitness and potential cardiac complications that could affect athletes taking nitrate supplementation.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".