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.
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“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]
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“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.”
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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
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