The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension
Abstract
AIMS: Reduced bioavailability of endogenous nitric oxide (NO) is a central pathophysiological event in hypertension and other cardiovascular diseases. Recently, it was demonstrated that inorganic nitrate from dietary sources is converted in vivo to form nitrite, NO, and other bioactive nitrogen oxides. We tested the hypothesis that dietary inorganic nitrate supplementation may have therapeutic effects in a model of renal and cardiovascular disease. METHODS AND RESULTS: Sprague-Dawley rats subjected to unilateral nephrectomy and chronic high-salt diet from 3 weeks of age developed hypertension, cardiac hypertrophy and fibrosis, proteinuria, and histological as well as biochemical signs of renal damage and oxidative stress. Simultaneous nitrate treatment (0.1 or 1 mmol nitrate kg⁻¹ day⁻¹), with the lower dose resembling the nitrate content of a diet rich in vegetables, attenuated hypertension dose-dependently with no signs of tolerance. Nitrate treatment almost completely prevented proteinuria and histological signs of renal injury, and the cardiac hypertrophy and fibrosis were attenuated. Mechanistically, dietary nitrate restored the tissue levels of bioactive nitrogen oxides and reduced the levels of oxidative stress markers in plasma (malondialdehyde) and urine (Class VI F2-isoprostanes and 8-hydroxy-2-deoxyguanosine). In addition, the increased circulating and urinary levels of dimethylarginines (ADMA and SDMA) in the hypertensive rats were normalized by nitrate supplementation. CONCLUSION: Dietary inorganic nitrate is strongly protective in this model of renal and cardiovascular disease. Future studies will reveal if nitrate contributes to the well-known cardioprotective effects of a diet rich in vegetables.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Carlström et al., showed that dietary nitrate increased the tissue levels of nitrite and S-nitrosothiols in the heart, and attenuated oxidative stress and prevented cardiac injury in Sprague-Dawley rats subjected to unilateral nephrectomy and a high-salt diet [37].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [37]
In the citing paper
“In addition, nitrate supplementation offered cardioprotection against doxorubicin-induced cardiomyopathy 37 and prevented oxidative stress and cardiovascular and renal injury in salt-induced hypertension.39”
From Dietary nitrate supplementation improves revascularization in chronic ischemia (2012) · cites this paper as [39]
Citations
Cites
The L-Arginine-Nitric Oxide Pathway
Epstein, F. H., Moncada, S., & Higgs, A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292706 · Cited by 6,678
A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure
Appel, L. J., Moore, T. J., Obarzanek, E., Vollmer, W. M., Svetkey, L. P., Sacks, F. M., Bray, G. A., Vogt, T. M., Cutler, J. A., Windhauser, M. M., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704173361601 · Cited by 5,981
Sacks, F. M., Svetkey, L. P., Vollmer, W. M., Appel, L. J., Bray, G. A., Harsha, D., Obarzanek, E., Conlin, P. R., Miller, E. R., Simons-Morton, D. G., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200101043440101 · Cited by 5,638
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 1×
“and nitrosyl products.(14) The levels of nitrate and other nitrogen oxide species were measured in plasma and tissues after 10 weeks of dietary supplementation with nitrate.”
BackgroundSelf-citationEndothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace
Förstermann, U., & Münzel, T. (2006) · Circulation · doi:10.1161/circulationaha.105.602532 · Cited by 1,957 · cited 1×
“Nitric oxide (NO) is a key regulator of cardiovascular homeostasis with reduced NO bioavailability being a central underlying pathological event in many cardiovascular disorders including hypertension and atherosclerosis.(7,8) An increase in renal and vascular oxidative stress is thought to be involved in salt-induced…”
BackgroundSalt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies
Strazzullo, P., D'Elia, L., Kandala, N.-B., & Cappuccio, F. P. (2009) · BMJ · doi:10.1136/bmj.b4567 · Cited by 1,580
The Effect of Fruit and Vegetable Intake on Risk for Coronary Heart Disease
Joshipura, K. J., Hu, F. B., Manson, J. E., Stampfer, M. J., Rimm, E. B., Speizer, F. E., Colditz, G., Ascherio, A., Rosner, B., Spiegelman, D., et al. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-12-200106190-00010 · Cited by 1,396
Projected effect of dietary salt reductions on future cardiovascular disease
Bibbins-Domingo, K., Chertow, G. M., Coxson, P. G., Moran, A., Lightwood, J. M., Pletcher, M. J., & Goldman, L. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907355 · Cited by 1,253
Fruit and Vegetable Intake in Relation to Risk of Ischemic Stroke
Joshipura, K. J. (1999) · JAMA · doi:10.1001/jama.282.13.1233 · Cited by 1,078
Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.103523 · Cited by 1,078
Cited by
Sorted by citations
Graves, D. B. (2012) · Journal of Physics D Applied Physics · doi:10.1088/0022-3727/45/26/263001 · Cited by 1,534
Strategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576
Self-citationRenal Autoregulation in Health and Disease
Carlström, M., Wilcox, C. S., & Arendshorst, W. J. (2015) · Physiological Reviews · doi:10.1152/physrev.00042.2012 · Cited by 485
Self-citationRochette, L., Lorin, J., Zeller, M., Guilland, J.-C., Lorgis, L., Cottin, Y., & Vergely, C. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.07.004 · Cited by 456
“Increasing bioactive NO by oral administration of nitrate prevented ROS and restored normal levels of ADMA in a rat model of salt-sensitive hypertension (Carlstrom et al., 2011); dietary nitrate attenuated the level of OS.”
BackgroundMetabolic Effects of Dietary Nitrate in Health and Disease
Lundberg, J. O., Carlström, M., & Weitzberg, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.007 · Cited by 374
Self-citation
Metadata
- Authors
- Carlström, M., Persson, A. E. G., Larsson, E., Hezel, M., Scheffer, P. G., Teerlink, T., Weitzberg, E., & Lundberg, J. O.
- Affiliations
- Uppsala University (SE)
- Karolinska Institutet (SE)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Carlström, Mattias
- Weitzberg, Eddie
- Lundberg, Jon O.
- ORCID
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11-19
- Volume
- 89
- Issue
- 3
- Pages
- 574-585
- ISSN
- 0008-6363 (ISSN-L)
- 1755-3245
- OpenAlex
- W1974569195
- Semantic Scholar
- b3bf26b82cdbdf00b0fade39de86bb83ed79872b
- Cited by
- 261
- References
- 55
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 10 · 2021: 11 · 2020: 16 · 2019: 13 · 2018: 25 · 2017: 31 · 2016: 22 · 2015: 23 · 2014: 22 · 2013: 20 · 2012: 20
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wenner-Gren Foundation
- Massachusetts General Hospital
- Vrije Universiteit Amsterdam
- Svenska Sällskapet för Medicinsk Forskning
- Karolinska Institutet
- Vetenskapsrådet
- Magnus Bergvalls Stiftelse
- Svenska Läkaresällskapet
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- dietary nitrate, nitric oxide bioavailability, salt-induced hypertension, oxidative stress, kidney injury, cardiac hypertrophy, myocardial fibrosis, proteinuria, dimethylarginines, asymmetric dimethylarginine, SDMA, malondialdehyde, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, high-salt diet, cardioprotection
- MeSH terms
- Animals, Arginine, Blood Pressure, Disease Models, Animal, Cardiomegaly, Hypertension, Renal, Kidney, Male, Nephrectomy, Nitrates, Nitric Oxide, Nitrogen, Proteinuria, Rats, Sprague-Dawley, Sodium Chloride, Dietary, Oxidative Stress, Rats
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 ›
Are you an author, or do you see a problem with this page? Request a review
