Impact of dietary nitrate on age-related diastolic dysfunction
Open accessAbstract
AIMS: Diastolic dysfunction is highly prevalent, and ageing is the main contributor due to impairments in active cardiac relaxation, ventriculo-vascular stiffening, and endothelial dysfunction. Nitric oxide (NO) affects cardiovascular functions, and NO bioavailability is critically reduced with ageing. Whether replenishment of NO deficiency with dietary inorganic nitrate would offer a novel approach to reverse age-related cardiovascular alterations was not known. METHODS AND RESULTS: A dietary nitrate supplementation was applied to young (6 month) and old (20 month) wild-type mice for 8 weeks and compared with controls. High-resolution ultrasound, pressure-volume catheter techniques, and isolated heart measurements were applied to assess cardiac diastolic and vascular functions. Cardiac manganese-enhanced magnetic resonance imaging was performed to study the effects of dietary nitrate on myocyte calcium handling. In aged mice with preserved systolic function, dietary nitrate supplementation improved LV diastolic function, arterial compliance, and coronary flow reserve. Mechanistically, improved cardiovascular functions were associated with an accelerated cardiomyocyte calcium handling and augmented NO/cyclic guanosine monophosphate/protein kinase G signalling, while enhanced nitrate reduction was related to age-related differences in the oral microbiome. CONCLUSION: Dietary inorganic nitrate reverses age-related LV diastolic dysfunction and improves vascular functions. Our results highlight the potential of a dietary approach in the therapy of age-related cardiovascular alterations.
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In heart failure and cardiomyopathy, dietary nitrate improves left ventricular function in mice and overall cardiac contractility and exercise performance in humans.
“Additionally, in the setting of heart failure and cardiomyopathy, dietary nitrate improves left ventricular function in mice[133] and overall cardiac contractility and exercise performance in humans[134–137]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [133]
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- Authors
- Rammos, C., Hendgen-Cotta, U. B., Totzeck, M., Pohl, J., Lüdike, P., Flögel, U., Deenen, R., Köhrer, K., French, B. A., Gödecke, A., Kelm, M., & Rassaf, T.
- Affiliations
- Essen University Hospital (DE)
- Heinrich Heine University Düsseldorf (DE)
- University of Virginia (US)
- Düsseldorf University Hospital (DE)
- Corresponding author
- Rassaf, Tienush
- ORCID
- Venue
- European Journal of Heart Failure
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-04-26
- Volume
- 18
- Issue
- 6
- Pages
- 599-610
- ISSN
- 1388-9842 (ISSN-L)
- 1879-0844
- OpenAlex
- W2343168506
- Cited by
- 31
- References
- 50
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 4
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Funders
- German Research Foundation (RA969/4-2], Ra969/7-2)
- Heine-Heine-University Forschungskommission
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- dietary nitrate, inorganic nitrate supplementation, diastolic dysfunction, aging, nitric oxide bioavailability, left ventricular diastolic function, arterial compliance, coronary flow reserve, cardiomyocyte calcium handling, oral microbiota, nitrate reduction, vascular function, aged mice
- MeSH terms
- Aging, Animals, Calcium, Coronary Vessels, Diastole, Echocardiography, Endothelium, Vascular, Hemodynamics, Magnetic Resonance Imaging, Male, Mouth, Nitrates, Ventricular Function, Left, Dietary Supplements, Myocytes, Cardiac, Mice, Vascular Stiffness, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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