The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; none of the 2 sources its claims cite is checked for support yet.
Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice
Open accessAbstract
The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate–nitrite–NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.
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TL;DR
Dietary sodium nitrate supplementation in eNOS-deficient mice increased bioactive nitrogen oxides and reversed several features of metabolic syndrome, including visceral fat, circulating triglycerides, and a prediabetic glucose phenotype. Chronic nitrate also lowered blood pressure in rats, with the effect still present during NOS inhibition.
Key findings
- Acute nitrate (0.1 mmol·kg−1 i.p.) increased plasma nitrite and tissue nitros(yl)ation products in eNOS-deficient mice; chronic nitrate increased tissue S-nitrosothiols/nitros(yl)ation products without significantly changing plasma/tissue nitrate and nitrite versus controls.
- In aged eNOS−/− mice, chronic sodium nitrate (0.1 mmol·kg−1·d−1; 85 mg·L−1, 1 mM in drinking water for 8–10 wk) reduced body weight over a 7-wk observation period, reduced visceral fat, and lowered circulating triglycerides.
- After 10 wk of nitrate supplementation, glucose tolerance was almost normalized in eNOS−/− mice; fasting blood glucose, HbA1c, and the proinsulin/insulin ratio were lower than in untreated eNOS−/− mice. Nitrate had no effect on glucose tolerance in young wild-type or nNOS-deficient mice.
- In rats, chronic nitrate (same dose for 8 wk) lowered mean arterial pressure throughout a 3-d observation period, and this difference persisted after L-NAME (1 g·L−1); L-NAME’s pressor effect was delayed by 12 h in nitrate-treated animals. No firm evidence of increased mitochondrial biogenesis or tissue cGMP was found.
Methods
- Aged eNOS-deficient mice (mean 16 mo, range 14–22 mo) were randomized to sodium nitrate in drinking water (85 mg·L−1, 1 mM) for 8–10 wk or control; acute experiments used 0.1 mmol·kg−1 i.p. Rats received the same nitrate dose for 8 wk for telemetric blood pressure measurements, followed by L-NAME (1 g·L−1).
- Nitrate, nitrite, and nitros(yl)ation products were measured by chemiluminescence. Glucose tolerance tests were performed after 14 h fasting with i.p. glucose (2 g·kg−1); HbA1c, insulin, and proinsulin were measured after 14 h fasting. Body weight was recorded weekly for 7 wk; visceral adipose tissue and triglycerides were measured at termination.
- Statistics used mean ± SEM with 5–15 animals per group; two-tailed independent Student’s t test, ANOVA with Bonferroni or Dunnett’s post hoc tests, and P < 0.05 considered significant.
Limitations
- The paper states that the reason for the 12-h delay in the L-NAME blood-pressure response in nitrate-treated rats is not known, and that the importance of enterosalivary nitrate cycling and bacteria-derived nitrite formation in mice is yet to be determined.
- The paper states that long-term human intervention studies are warranted and that the exact mechanisms underlying metabolic syndrome remain unsettled; it also notes that failure to detect increased tissue cGMP does not exclude cGMP-mediated effects.
- Evident from the text: findings are from animal models (aged eNOS-deficient mice and rats), not humans; sample sizes were modest (5–15 per group), and the eNOS-deficient model may not fully represent human metabolic syndrome.
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6 Own interpretation · 3 Own result · 2 Own method · 1 Not checked yet
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions.”
- Also stated in: § Discussion · plain
“The results presented herein show that dietary supplementation with inorganic nitrate attenuates several features of metabolic syndrome in aged eNOS-deficient mice.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The effects of sodium nitrate are attributable to nitrate rather than to sodium or other components of the treatment.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With chronic low-dose administration of nitrate, plasma and tissue levels of nitrate and nitrite were not significantly different from those seen in control animals receiving no nitrate supplementation.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Results > Formation of Bioactive Nitrogen Oxides from Dietary Nitrate.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The effects of sodium nitrate are attributable to nitrate rather than to sodium or other components of the treatment.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This finding indicates that at least some of the observed metabolic effects of nitrate are cGMP-independent.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The present findings are highly relevant from a nutritional perspective as well, as the amount of nitrate used is readily achievable via a normal diet.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, in addition to the second-by-second regulation of vascular tone by eNOS-derived NO, its oxidized end-product nitrate may serve as a long-lived reservoir for NO-like bioactivity in tissues.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 4
- Probably not a substantial claim. 4
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present study, we failed to detect an increase in tissue cGMP formation after nitrate, but we did detect significant formation of nitros(yl)ation products, including S-nitrosothiols, in the tissues after nitrate administration.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The effects of sodium nitrate are attributable to nitrate rather than to sodium or other components of the treatment.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that this very modest amount had such profound biological effects supports the intriguing possibility that endogenous nitrate levels are already sufficient to affect cellular processes.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The reason for this is not known, but apparently NOS-independent NO formation seemed to have prevented the initial blood-pressure response during NOS inhibition.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Results > Blood Pressure.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The eNOS-deficient mice were obtained from Jackson Laboratories and were randomly assigned to treatment groups to ensure that each group had the same average age (mean 16 mo, range 14–22 mo) and weight.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Materials and Methods > Animals.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“All animal work was conducted in accordance with the Swedish Animal Research Committee at Karolinska Institutet.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Materials and Methods > Animals.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“This result is consistent with the theory that metabolic effects of nitrate might be related to a reduction in oxidative stress, which is indeed absent or less pronounced in these mice.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Ingested nitrate is rapidly absorbed in the small intestine, then actively taken up by the salivary glands and concentrated in saliva.”
§ Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice > Discussion
What the sources say
- Not checked yetcites [18] Lundberg JO, Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med. 2004;37:395–400. doi: 10.1016/j.freeradbiomed.2004.04.027. [[DOI](https://doi.org/10.1016/j.freeradbiomed.2004.04.027)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15223073/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Free%20Radic%20Biol%20Med&title=Inorganic%20nitrate%20is%20a%20possible%20source%20for%20systemic%20generation%20of%20nitric%20oxide&author=JO%20Lundberg&author=M%20Govoni&volume=37&publication_year=2004&pages=395-400&pmid=15223073&do source
- Not checked yetcites [22] Gladwin MT, et al. The emerging biology of the nitrite anion. Nat Chem Biol. 2005;1:308–314. doi: 10.1038/nchembio1105-308. [[DOI](https://doi.org/10.1038/nchembio1105-308)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16408064/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Nat%20Chem%20Biol&title=The%20emerging%20biology%20of%20the%20nitrite%20anion&author=MT%20Gladwin&volume=1&publication_year=2005&pages=308-314&pmid=16408064&doi=10.1038/nchembio1105-308&)] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The effects of sodium nitrate are attributable to nitrate rather than to sodium or other components of the treatment.
“NaNO3 was added to the drinking water during 8 to 10 wk at a concentration of 85 mg·L−1 (1 mM).”
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
“the therapeutic potential of dietary nitrate/nitrite has been supported by recent studies demonstrating the improvements of insulin resistance in humans and animals as a result of its enhancing the NO availability in plasma and tissues [65,66,67,68].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [66]
In the citing paper
“the endogenous production of nitrate from NO oxidation (mainly via reaction with oxy-hemoglobin) has long been recognized to be an order of magnitude greater than dietary intake as shown in the late 1970s [7] and more recently in studies using eNOS-deficient mice [45].”
From Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions (2015) · cites this paper as [45]
In the citing paper
“NOS3 dependent NO production plays an important role in regulating steady state plasma nitrite levels, while also influencing nitrate, nitroso, and nitrosyl products in tissues [72, 73].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [72]
In the citing paper
“Recent work from Carlström et al reveals that long term dietary nitrate consumption can reverse metabolic parameters associated with eNOS dysfunction that are associated with the development of cardiovascular disease [72].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [72]
In the citing paper
“It was found that daily administration of 85 mg/L−1 in the drinking water for 8–10 weeks decreased body weight, plasma triglycerides, and visceral fat while improving glucose tolerance and fasting blood glucose levels in eNOS deficient mice.”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [72]
Citations
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
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
Eckel, R. H., Alberti, K., Grundy, S. M., & Zimmet, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61794-3 · Cited by 6,317
Eckel, R. H., Grundy, S. M., & Zimmet, P. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66378-7 · Cited by 5,755
Abdominal obesity and metabolic syndrome
Després, J.-P., & Lemieux, I. (2006) · Nature · doi:10.1038/nature05488 · Cited by 4,354
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 7×
“This result would be mechanistically similar to the earlier proposed role of S-nitrosothiols (23) or nitrite (10) as stable carriers and transducers of NO-like bioactivity in blood.”
BackgroundResultInfluentialSelf-citationMetabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
Jia, L., Bonaventura, C., Bonaventura, J., & Stamler, J. S. (1996) · Nature · doi:10.1038/380221a0 · Cited by 1,592
Stamler (2001) · doi:10.1016/s0092-8674(01)00495-0 · Cited by 1,261
Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Nisoli, E., Clementi, E., Paolucci, C., Cozzi, V., Tonello, C., Sciorati, C., Bracale, R., Valerio, A., Francolini, M., Moncada, S., et al. (2003) · Science · doi:10.1126/science.1079368 · Cited by 1,243
Grundy, S. M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5839-6_1 · Cited by 1,227
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103
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
Brown, G. C., & Cooper, C. E. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01290-3 · Cited by 1,055
Diet and Health: What Should We Eat?
Willett, W. C. (1994) · Science · doi:10.1126/science.8160011 · Cited by 1,008
Nitrate, bacteria and human health
Lundberg, J. O., Weitzberg, E., Cole, J. A., & Benjamin, N. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro929 · Cited by 739
Self-citationCarter, P., Gray, L. J., Troughton, J., Khunti, K., & Davies, M. J. (2010) · BMJ · doi:10.1136/bmj.c4229 · Cited by 728
Inorganic nitrate is a possible source for systemic generation of nitric oxide
Lundberg, J. O., & Govoni, M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.04.027 · Cited by 657
Self-citationEffects of dietary nitrate on oxygen cost during exercise
Larsen, F. J., Weitzberg, E., Lundberg, J. O., & Ekblom, B. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01713.x · Cited by 637
Self-citationInorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO
Kapil, V., Milsom, A. B., Okorie, M., Maleki-Toyserkani, S., Akram, F., Rehman, F., Arghandawi, S., Pearl, V., Benjamin, N., Loukogeorgakis, S., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.153536 · Cited by 621
Nitrate and nitrite in biology, nutrition and therapeutics
Lundberg, J. O., Gladwin, M. T., Ahluwalia, A., Benjamin, N., Bryan, N. S., Butler, A., Cabrales, P., Fago, A., Feelisch, M., Ford, P. C., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.260 · Cited by 617
Self-citationThe emerging biology of the nitrite anion
Gladwin, M. T., Schechter, A. N., Kim-Shapiro, D. B., Patel, R. P., Hogg, N., Shiva, S., Cannon, R. O., Kelm, M., Wink, D. A., Espey, M. G., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio1105-308 · Cited by 609
Self-citationWebb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608 · cited 1×
“Administration of nitrate or nitrite (NO2 ) to humans and rodents is clearly associated with NO-like bioactivity, as demonstrated by increases in cGMP formation (12), vasodilatation (13, 14), reduction in blood pressure (15), inhibition of platelet function (16), and protection against ischemia-reperfusion injury (17).”
BackgroundGovoni, M., Jansson, E. Å., Weitzberg, E., & Lundberg, J. O. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.08.003 · Cited by 602
Self-citationEffects of Dietary Nitrate on Blood Pressure in Healthy Volunteers
Larsen, F. J., Ekblom, B., Sahlin, K., Lundberg, J. O., & Weitzberg, E. (2006) · New England Journal of Medicine · doi:10.1056/nejmc062800 · Cited by 587
Self-citationPlasma nitrite reflects constitutive nitric oxide synthase activity in mammals
Kleinbongard, P., Dejam, A., Lauer, T., Rassaf, T., Schindler, A., Picker, O., Scheeren, T., Gödecke, A., Schrader, J., Schulz, R., et al. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00406-4 · Cited by 586
Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes
Mogensen, M., Sahlin, K., Fernström, M., Glintborg, D., Vind, B. F., Beck-Nielsen, H., & Højlund, K. (2007) · Diabetes · doi:10.2337/db06-0981 · Cited by 573
Shiva, S., Sack, M. N., Greer, J. J., Duranski, M., Ringwood, L. A., Burwell, L., Wang, X., MacArthur, P. H., Shoja, A., Raghavachari, N., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070198 · Cited by 555
Duplain, H., Burcelin, R., Sartori, C., Cook, S., Egli, M., Lepori, M., Vollenweider, P., Pedrazzini, T., Nicod, P., Thorens, B., et al. (2001) · Circulation · doi:10.1161/01.cir.104.3.342 · Cited by 533
Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues
Bryan, N. S., Fernandez, B. O., Bauer, S. M., Garcia-Saura, M. F., Milsom, A. B., Rassaf, T., Maloney, R. E., Bharti, A., Rodriguez, J., & Feelisch, M. (2005) · Nature Chemical Biology · doi:10.1038/nchembio734 · Cited by 518
eNOS, metabolic syndrome and cardiovascular disease
Huang, P. L. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.03.005 · Cited by 365
A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis
Jansson, E. Å., Huang, L., Malkey, R., Govoni, M., Nihlén, C., Olsson, A., Stensdotter, M., Petersson, J., Holm, L., Weitzberg, E., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.92 · Cited by 356
Self-citationLiese, A. D., Nichols, M., Sun, X., D'Agostino, R. B., & Haffner, S. M. (2009) · Diabetes Care · doi:10.2337/dc09-0228 · Cited by 256
Petersson, J., Carlström, M., Schreiber, O., Phillipson, M., Christoffersson, G., Jägare, A., Roos, S., Jansson, E. Å., Persson, A. E. G., Lundberg, J. O., et al. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.01.011 · Cited by 235
Self-citationMonti, L. D., Barlassina, C., Citterio, L., Galluccio, E., Berzuini, C., Setola, E., Valsecchi, G., Lucotti, P., Pozza, G., Bernardinelli, L., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.5.1270 · Cited by 195
Covalent Peroxisome Proliferator-activated Receptor γ Adduction by Nitro-fatty Acids
Schopfer, F. J., Cole, M. P., Groeger, A. L., Chen, C.-S., Khoo, N. K. H., Woodcock, S. R., Golin-Bisello, F., Motanya, U. N., Li, Y., Zhang, J., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.091512 · Cited by 171
Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice
Egli, M., Vollenweider, P., Burcelin, R., Nicod, P., & Thorens, B. (2003) · Swiss Medical Weekly · doi:10.4414/smw.2003.10239 · Cited by 156
Nitrate and gastric cancer risks
TANNENBAUM, S. R., & CORREA, P. (1985) · Nature · doi:10.1038/317675b0 · Cited by 96
Association of NOS3 gene with metabolic syndrome in hypertensive patients
Fernández, M., Ruiz, R., Gonzalez, M., Ramírez‐Lorca, R., Couto, C., Ramos, A., Gutierrez-Tous, R., de Rivera, J. M. P. S., Ruiz, A., Grilo, A., et al. (2004) · Thrombosis and Haemostasis · doi:10.1160/th04-02-0103 · Cited by 55
A technique to estimate the rate of whole body nitric oxide formation in conscious mice
Wickman, A., Klintland, N., Gan, L., Sakinis, A., Söderling, A., Bergström, G. M. L., & Caidahl, K. (2003) · Nitric Oxide · doi:10.1016/j.niox.2003.09.001 · Cited by 17
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Wu, Y., Ding, Y., Tanaka, Y., & Zhang, W. (2014) · International Journal of Medical Sciences · doi:10.7150/ijms.10001 · Cited by 1,420
Nitric oxide signaling in health and disease
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Metadata
- Authors
- Carlström, M., Larsen, F. J., Nyström, T., Hezel, M., Borniquel, S., Weitzberg, E., & Lundberg, J. O.
- Affiliations
- Uppsala University (SE)
- Karolinska Institutet (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-09-27
- Volume
- 107
- Issue
- 41
- Pages
- 17716-17720
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2955084
- OpenAlex
- W2074172668
- Cited by
- 382
- References
- 43
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 18 · 2023: 21 · 2022: 24 · 2021: 15 · 2020: 31 · 2019: 22 · 2018: 25 · 2017: 33 · 2016: 33 · 2015: 30 · 2014: 31 · 2013: 22 · 2012: 29
- FWCI
- 16.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wenner-Gren Foundation
- European Commission
- Kommunfullmäktige, Stockholms Stad
- Karolinska Institutet
- Vetenskapsrådet
- 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 › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Keywords
- dietary nitrate, sodium nitrate, metabolic syndrome, endothelial nitric oxide synthase, nitrate-nitrite-NO pathway, visceral fat accumulation, triglycerides, prediabetes, blood pressure, cardiovascular disease prevention, type 2 diabetes, eNOS-deficient mice
- MeSH terms
- Analysis of Variance, Animals, Blood Pressure, Body Weight, Mice, Mutant Strains, Nitrates, Nitrogen Oxides, Triglycerides, Dietary Supplements, Metabolic Syndrome, Intra-Abdominal Fat, Mice, Rats, Nitric Oxide Synthase Type III
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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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.
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