Inorganic nitrite therapy: historical perspective and future directions

In the paper

“Importantly, during inflammatory reactions or infection involving increased iNOS expression large amounts of NO are produced resulting in significant increases in plasma nitrate and nitrite [42–44].”

What the sources say

• Partly supported

  The Abstract and Results report significantly increased plasma nitrate in infective gastroenteritis, consistent with increased NO production. But the Results say most patients with inflammatory bowel disease did not have increased plasma nitrate, and the paper does not establish increased plasma nitrite or iNOS expression as the cause of the measured rise. Page numbers were not supplied for these passages. (LLM, conf=0.89)

  cites [42] Dykhuizen RS Masson J McKnight G Mowat AN Smith CC Smith LM Benjamin N Plasma nitrate concentration in infective gastroenteritis and inflammatory bowel disease Gut 39 393 395 1996 8949643 PMC1383345 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction describes a cytokine-inducible pathway that produces high levels of NO, and the Results report a significant rise in serum nitrate during IL-2 therapy. The paper does not establish that both plasma nitrate and plasma nitrite rise during inflammatory reactions or infection; its measured human setting was IL-2 treatment. (LLM, conf=0.85)

  cites [43] Hibbs JB Jr Westenfelder C Taintor R Vavrin Z Kablitz C Baranowski RL Ward JH Menlove RL McMurry MP Kushner JP Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy The Journal of clinical investigation 89 867 877 1992 1541678 PMC442932 sourceExperimental — accuracy not yet measured
• Not checked yetcites [44] Shi Y Li HQ Shen CK Wang JH Qin SW Liu R Pan J Plasma nitric oxide levels in newborn infants with sepsis J Pediatr 123 435 438 1993 8355123 source

In the paper

“It was also shown that the addition of NO to blood generates significant concentrations of plasma nitrite that involved copper oxidation, which was found to be ceruloplasmin dependent NO oxidation [78, 79].”

What the sources say

• Not checked yetcites [78] Shiva S WX Ringwood LA Xu X Yuditskaya S Annavajjhala V Miyajima H Hogg N Harris ZL Gladwin MT Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis Nat Chem Biol 2 486 493 2006 16906150 source
• Partly supported

  The Results report that about 30% of added NO below 2 μM formed nitrite in plasma, supporting the nitrite-formation part of the claim. They describe the possible NO oxidase pathway as “likely metal-based,” but do not identify copper or establish ceruloplasmin dependence. (LLM, conf=0.90)

  cites [79] Wang X Tanus-Santos JE Reiter CD Dejam A Shiva S Smith RD Hogg N Gladwin MT Biological activity of nitric oxide in the plasmatic compartment Proceedings of the National Academy of Sciences of the United States of America 101 11477 11482 2004 15258287 PMC509225 sourceExperimental — accuracy not yet measured

In the paper

“However, now it is clear that nitrite anion is recycled back to NO in multiple ways.”

What the sources say

• Supported

  The Abstract says nitrite can be recycled back to bioactive NO in blood and tissues and that its reduction occurs through several routes. The “Nitrite Reduction to NO In Vivo” section also describes several alternative pathways for generating NO from nitrite. (LLM, conf=0.94)

  cites [73] Lundberg JO Weitzberg E NO generation from nitrite and its role in vascular control Arteriosclerosis, thrombosis, and vascular biology 25 915 922 2005 15746440 source
• Supported

  The Introduction states that nitrite can be recycled to produce NO in various ways and lists several mechanisms, including mitochondrial electron transport, protonation, deoxyhemoglobin, and xanthine oxidase. This directly supports the paraphrase. (LLM, conf=0.94)

  cites [82] Bryan NS Grisham MB Methods to detect nitric oxide and its metabolites in biological samples Free radical biology & medicine 43 645 657 2007 17664129 PMC2041919 source
• Supported

  The Introduction says nitrite, once considered an inert NO metabolite, can be reduced back to NO. The Clinical Translation section identifies ischemia, hypoxia, and low pH as conditions under which nitrite releases NO, supporting the broad claim that this occurs in multiple ways. (LLM, conf=0.86)

  cites [83] Calvert JW Lefer DJ Clinical translation of nitrite therapy for cardiovascular diseases Nitric Oxide 22 91 97 2010 19909823 PMC3263353 source

In the paper

“Shiva et al elegantly demonstrated that nitrite therapy significantly blunted mitochondrial uncoupling during in vivo ischemia reperfusion through nitrite mediated, NO dependent, inhibition of mitochondrial complex I activity [40].”

What the sources say

• Partly supported

  The Results sections “Nitrite inhibits complex I after I/R” and “Nitrite-dependent protection occurs at the mitochondrial level” support NO-dependent complex I inhibition and improved post-anoxia ATP recovery after nitrite treatment. They do not establish that nitrite significantly blunted mitochondrial uncoupling during in vivo I/R; the paper says ATP formation was measured to exclude uncoupling as a major explanation for the differing respiratory rates. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites [40] Shiva S Sack MN Greer JJ Duranski M Ringwood LA Burwell L Wang X MacArthur PH Shoja A Raghavachari N Calvert JW Brookes PS Lefer DJ Gladwin MT Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer J Exp Med 204 2089 2102 2007 17682069 PMC2118713 sourceExperimental — accuracy not yet measured

In the paper

“nitrite mediated changes in blood flow and endothelial cell growth were blocked by the NO scavenger cPTIO”

What the sources say

• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source

In the paper

“delayed sodium nitrite therapy 5 days after ischemic induction still augments ischemic tissue reperfusion and arteriogenesis development (Pattillo in press).”

What the sources say

• Not checked yetcites Pattillo in press

In the paper

“nitrite therapy significantly increased ischemic tissue nitrite/nitrosothiol levels”

What the sources say

• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source

In the paper

“sodium nitrate therapy was unable to mediate similar responses to nitrite therapy over the duration of study”

What the sources say

• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source

In the paper

“administration of a single dose of sodium nitrite after induction of ischemia did not augment hind limb reperfusion (unpublished observations)”

In the paper

“Our group has reported that continuous sodium nitrite administration increases ischemic hind limb blood flow after permanent femoral artery ligation.”

What the sources say

• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source

In the paper

“nitrite therapy selectively induced endothelial cell proliferation and angiogenesis only in the ischemic limb”

What the sources say

• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source

In the paper

“we found that dipyridamole therapy significantly increased contralateral non-ischemic limb eNOS activity and NO production that increased plasma nitrite levels to augment ischemic limb reperfusion and angiogenesis [170].”

What the sources say

• Not checked yetcites [170] Venkatesh PK Pattillo CB Branch B Hood J Thoma S Illum S Pardue S Teng X Patel RP Kevil CG Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite/nitric oxide-dependent pathway Cardiovascular research 85 661 670 2010 20061326 PMC2819839 source

In the paper

“Interestingly, sodium nitrite therapy in the hind limb ischemia model strongly depressed interleukin-10 (IL-10) expression.”

What the sources say

• Not checked yetcites [252] Pattillo CB Fang K Terracciano J Kevil CG Reperfusion of chronic tissue ischemia: nitrite and dipyridamole regulation of innate immune responses Annals of the New York Academy of Sciences 1207 83 88 2010 20955430 PMC4414240 source

In the paper

“We found that nitrite anion therapy in chronically ischemic tissue results in selective down regulation of innate immune response genes such as chemokine ligands, toll like receptors, and leukotriene and formyl peptide receptors, while increasing expression of VE cadherin.”

What the sources say

• Not checked yetcites [252] Pattillo CB Fang K Terracciano J Kevil CG Reperfusion of chronic tissue ischemia: nitrite and dipyridamole regulation of innate immune responses Annals of the New York Academy of Sciences 1207 83 88 2010 20955430 PMC4414240 source

In the paper

“Indeed, the recent study by Hunault et al examining oral sodium nitrite pharmacokinetics and dynamics along with changes in blood pressure and methemoglobin levels was not found on the clinical trials website [69].”

What the sources say

• Not checked yetcites [69] Hunault CC van Velzen AG Sips AJ Schothorst RC Meulenbelt J Bioavailability of sodium nitrite from an aqueous solution in healthy adults Toxicology letters 190 48 53 2009 19576277 source

In the paper

“However, the number of clinical trials involving sodium nitrite therapy is relatively small reflecting that this endeavor has a long way to go before the field begins to fully appreciate the clinical utility of this molecule.”

In the paper

“More recent studies also indicate that sodium nitrate may also increase plasma nitrite levels via the enterosalivary circulatory system resulting in nitrate reduction to nitrite by microorganisms found within the oral cavity.”

In the paper

“These discoveries have led to renewed hope and efforts for an effective NO based therapeutic agent through the unique action of sodium nitrite as an NO pro-drug.”

In the paper

“However studies conducted in this area over the last few years have unraveled mechanisms by which NO bioactivity in blood and in tissue have been preserved in the form of nitrite, nitrate, S-nitrosothiols (RSNO), N-nitrosamines (RNNO), nitrosylhemoglobin (NOHb), and S-nitrosohemoglobin (SNOHb) [16–21].”

What the sources say

• Not checked yetcites [16] Stamler JS Jaraki O Osborne J Simon DI Keaney J Vita J Singel D Valeri CR Loscalzo J Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin Proceedings of the National Academy of Sciences of the United States of America 89 7674 7677 1992 1502182 PMC49773 source
• Not checked yetcites [17] Kleinbongard P Dejam A Lauer T Rassaf T Schindler A Picker O Scheeren T Godecke A Schrader J Schulz R Heusch G Schaub GA Bryan NS Feelisch M Kelm M Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals Free radical biology & medicine 35 790 796 2003 14583343 source
• Not checked yetcites [18] Gladwin MT WX Reiter CD Yang BK Vivas EX Bonaventura C Schechter AN S-nitrosohemoglobin is unstable in the reductive red cell environment and lacks O2/NO-linked allosteric function The Journal of biological chemistry 277 27818 27828 2002 12023289 source
• Not checked yetcites [19] Cosby K Partovi KS Crawford JH Patel RP Reiter CD Martyr S Yang BK Waclawiw MA Zalos G Xu X Huang KT Shields H Kim-Shapiro DB Schechter AN Cannon RO 3rd Gladwin MT Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nature medicine 9 1498 1505 2003 14595407 source
• Not checked yetcites [20] Bryan NS Rassaf T Maloney RE Rodriguez CM Saijo F Rodriguez JR Feelisch M Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo Proceedings of the National Academy of Sciences of the United States of America 101 4308 4313 2004 15014175 PMC384737 source
• Not checked yetcites [21] McMahon TJ Doctor A Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin Proc Am Thorac Soc 3 153 160 2006 16565424 PMC2658680 source

In the paper

“Although NO is known to protect tissues from ischemic injury, the ability of nitric oxide synthases to generate NO during ischemia is compromised because of the requirement for oxygen, BH4, and other co-factors which may be limiting during tissue ischemia [29–31].”

What the sources say

• Not checked yetcites [29] Nakano A LG Heusch G Downey JM Cohen MV Exogenous nitric oxide can trigger a preconditioned state through a free radical mechanism, but endogenous nitric oxide is not a trigger of classical ischemic preconditioning J Mol Cell Cardiol 32 1159 1167 2000 10860760 source
• Not checked yetcites [30] Duranski MR Elrod JW Calvert JW Bryan NS Feelisch M Lefer DJ Genetic overexpression of eNOS attenuates hepatic ischemia-reperfusion injury American journal of physiology 291 H2980 2986 2006 16877550
• Not checked yetcites [31] Jones SP Bolli R The ubiquitous role of nitric oxide in cardioprotection J Mol Cell Cardiol 40 16 23 2006 16288777 source

In the paper

“However, there is now wide agreement and abundant experimental evidence that nitrite anion represents an important reservoir of NO bioequivalents to augment tissue NO levels during pathophysiological states where NO synthesis from enzymatic pathways may be unavailable.”

In the paper

“It has been reported that up to 70–90% of plasma nitrite is derived from eNOS activity in humans and rodents [17].”

What the sources say

• Not checked yetcites [17] Kleinbongard P Dejam A Lauer T Rassaf T Schindler A Picker O Scheeren T Godecke A Schrader J Schulz R Heusch G Schaub GA Bryan NS Feelisch M Kelm M Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals Free radical biology & medicine 35 790 796 2003 14583343 source

In the paper

“A report by Duncan et al has shown in rats that the reduction of salivary nitrate to nitrite occurs at a discrete posterior area of the tongue that is colonized by nitrate-reducing bacteria [54].”

What the sources say

• Not checked yetcites [54] Duncan C Dougall H Johnston P Green S Brogan R Leifert C Smith L Golden M Benjamin N Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate Nature medicine 1 546 551 1995 7585121 source

In the paper

“This has also been confirmed in pigs, where high concentrations of these nitrate-reducing bacteria are present on the posterior portion of the tongue [55].”

What the sources say

• Not checked yetcites [55] Li HDC Golden M Leifert C Wilson WSBA Hinton RH Identification of nitrate reducing bacteria from the oral cavity of pigs and rats Managing risks of nitrates to humans and the environment Cambridge, UK The Royal Society of Chemistry 1999 259 268

In the paper

“Conversely, nitrite is more concentrated within cells and tissues (low μM) compared to plasma [20, 46, 47].”

What the sources say

• Not checked yetcites [20] Bryan NS Rassaf T Maloney RE Rodriguez CM Saijo F Rodriguez JR Feelisch M Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo Proceedings of the National Academy of Sciences of the United States of America 101 4308 4313 2004 15014175 PMC384737 source
• Not checked yetcites [46] Dejam A Hunter CJ Pelletier MM Hsu LL Machado RF Shiva S Power GG Kelm M Gladwin MT Schechter AN Erythrocytes are the major intravascular storage sites of nitrite in human blood Blood 106 734 739 2005 15774613 PMC1895176 source
• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source

In the paper

“These findings suggest that nitrite reduction to NO may serve as a critical mechanism to maintain NO reservoirs during pathophysiological states to minimize tissue dysfunction or injury.”

In the paper

“In blood, NO reacts with oxygenated hemoglobin to yield nitrate and methemoglobin [77].”

What the sources say

• Not checked yetcites [77] Eich RF Li T Lemon DD Doherty DH Curry SR Aitken JF Mathews AJ Johnson KA Smith RD Phillips GN Jr Olson JS Mechanism of NO-induced oxidation of myoglobin and hemoglobin Biochemistry 35 6976 6983 1996 8679521 source

In the paper

“Earlier studies reported the half-life of NO2- in blood to be approximately 110 seconds; however, it is now clear that the half life of exogenously administered nitrite can range between 20–30 minutes thus making it a readily available buffering metabolite to maintain NO bioavailability [52, 68, 69].”

What the sources say

• Not checked yetcites [52] Tannenbaum SR Sinskey AJ Weisman M Bishop W Nitrite in human saliva. Its possible relationship to nitrosamine formation J Natl Cancer Inst 53 79 84 1974 4835100 source
• Not checked yetcites [68] Kelm M Nitric oxide metabolism and breakdown Biochimica et Biophysica Acta (BBA) - Bioenergetics 1411 273 289 1999 10320663 source
• Not checked yetcites [69] Hunault CC van Velzen AG Sips AJ Schothorst RC Meulenbelt J Bioavailability of sodium nitrite from an aqueous solution in healthy adults Toxicology letters 190 48 53 2009 19576277 source

In the paper

“Together, these facts demonstrate that NO/nitrite levels are regulated in a complex manner with several redundant pathways in order to maintain bioavailable NO equivalents.”

In the paper

“As such, nitrate dependent nitrite production is predominantly generated from the enterosalivary circulatory system delivery of nitrate to the oral cavity where it is reduced by commensal bacteria nitrate reductase activity present in the digestive system (Figure 2) [49–53].”

What the sources say

• Not checked yetcites [49] Goaz PW BH Nitrite reduction in whole saliva J Dent Res 40 355 365 1961 source
• Not checked yetcites [50] Lundberg JO Weitzberg E Cole JA Benjamin N Nitrate, bacteria and human health Nat Rev Microbiol 2 593 602 2004 15197394 source
• Not checked yetcites [51] Spiegelhalder B Eisenbrand G Preussmann R Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds Food Cosmet Toxicol 14 545 548 1976 1017769 source
• Not checked yetcites [52] Tannenbaum SR Sinskey AJ Weisman M Bishop W Nitrite in human saliva. Its possible relationship to nitrosamine formation J Natl Cancer Inst 53 79 84 1974 4835100 source
• Not checked yetcites [53] van Maanen JM van Geel AA Kleinjans JC Modulation of nitrate-nitrite conversion in the oral cavity Cancer Detect Prev 20 590 596 1996 8939344

In the paper

“The contribution of the commensal pathway is significant as decreasing bacterial load using antiseptic mouthwash or antibiotics can significantly diminish plasma nitrite levels [56].”

What the sources say

• Not checked yetcites [56] Govoni M Jansson EA Weitzberg E Lundberg JO The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash Nitric Oxide 19 333 337 2008 18793740 source

In the paper

“Deoxyhemoglobin plays a central role in the bioactivation of nitrite by reducing it to bioavailable NO under physiological and pathophysiological conditions like hypoxia.”

What the sources say

• Not checked yetcites [19] Cosby K Partovi KS Crawford JH Patel RP Reiter CD Martyr S Yang BK Waclawiw MA Zalos G Xu X Huang KT Shields H Kim-Shapiro DB Schechter AN Cannon RO 3rd Gladwin MT Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nature medicine 9 1498 1505 2003 14595407 source

In the paper

“Dietary intake of nitrate and to a lesser degree nitrite found in meats (through preservatives), certain vegetables, and water provide important exogenous sources of nitrite [50].”

What the sources say

• Not checked yetcites [50] Lundberg JO Weitzberg E Cole JA Benjamin N Nitrate, bacteria and human health Nat Rev Microbiol 2 593 602 2004 15197394 source

In the paper

“It has also been reported that nitrite mediated NO formation dynamically modulates mitochondrial function to resist cellular injury and prevent apoptosis allowing cells to recover from ischemic insult [39].”

What the sources say

• Not checked yetcites [39] Shiva S HZ Grubina R Sun J Ringwood LA MacArthur PH Xu X Murphy E Darley-Usmar VM Gladwin MT Deoxymyoglobin is a nitrite reducatse that generates nitric oxide and regulates mitochondrial respiration Circulation research 100 654 661 2007 17293481 source

In the paper

“Commensal bacteria may also participate in nitrite and nitrate reduction and NO bioavailability in mucosal tissues such as the gastrointestinal and urogenital tracts [50, 91].”

What the sources say

• Not checked yetcites [50] Lundberg JO Weitzberg E Cole JA Benjamin N Nitrate, bacteria and human health Nat Rev Microbiol 2 593 602 2004 15197394 source
• Not checked yetcites [91] Lundberg JO Carlsson S Engstrand L Morcos E Wiklund NP Weitzberg E Urinary nitrite: more than a marker of infection Urology 50 189 191 1997 9255286 source

In the paper

“Studies have shown that acidic disproportionation of nitrite occurs throughout the body [50, 84, 92].”

What the sources say

• Not checked yetcites [50] Lundberg JO Weitzberg E Cole JA Benjamin N Nitrate, bacteria and human health Nat Rev Microbiol 2 593 602 2004 15197394 source
• Not checked yetcites [84] Zweier JL Wang P Kuppusamy P Direct measurement of nitric oxide generation in the ischemic heart using electron paramagnetic resonance spectroscopy The Journal of biological chemistry 270 304 307 1995 7814391 source
• Not checked yetcites [92] Modin A Bjorne H Herulf M Alving K Weitzberg E Lundberg JO Nitrite-derived nitric oxide: a possible mediator of ‘acidic-metabolic’ vasodilation Acta Physiol Scand 171 9 16 2001 11350258

In the paper

“Enzymatic reduction can also occur by several different proteins throughout the cell such as xanthine oxidase and proteins within the mitochondria (cytochrome c oxidase), which contribute to NO production under ischemic conditions [39, 88–90].”

What the sources say

• Not checked yetcites [39] Shiva S HZ Grubina R Sun J Ringwood LA MacArthur PH Xu X Murphy E Darley-Usmar VM Gladwin MT Deoxymyoglobin is a nitrite reducatse that generates nitric oxide and regulates mitochondrial respiration Circulation research 100 654 661 2007 17293481 source
• Not checked yetcites [88] Walters CL Taylor AM Pig-Heart Myoglobin and Its Derivatives with Nitric Oxide Biochimica et biophysica acta 82 420 422 1964 14127975 source
• Not checked yetcites [89] Webb A Bond R McLean P Uppal R Benjamin N Ahluwalia A Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage Proceedings of the National Academy of Sciences of the United States of America 101 13683 13688 2004 15347817 PMC518813 source
• Not checked yetcites [90] Zhang Z Naughton D Winyard PG Benjamin N Blake DR Symons MC Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity Biochem Biophys Res Commun 249 767 772 1998 9731211 source

In the paper

“These observations indicate that moderately acidic environments are capable of reducing nitrite to NO thus maintaining bioavailability during tissue stress.”

In the paper

“Initial appreciation of nitrite reduction to NO in tissues came from Zweier et al demonstrating that ischemic myocardium can produce NO from nitrite [84].”

What the sources say

• Not checked yetcites [84] Zweier JL Wang P Kuppusamy P Direct measurement of nitric oxide generation in the ischemic heart using electron paramagnetic resonance spectroscopy The Journal of biological chemistry 270 304 307 1995 7814391 source

In the paper

“XO nitrite reduction to NO occurs at the molybdenum site with either NADH or xanthine serving as reducing substrates.”

In the paper

“This report demonstrated that physiological levels of nitrite relaxed rat aortic rings at a pH of 6.6, which can readily be observed in tissues during ischemia [92].”

What the sources say

• Not checked yetcites [92] Modin A Bjorne H Herulf M Alving K Weitzberg E Lundberg JO Nitrite-derived nitric oxide: a possible mediator of ‘acidic-metabolic’ vasodilation Acta Physiol Scand 171 9 16 2001 11350258

In the paper

“Acidic disproportionation of nitrite can lead to increased levels of NO [84–86].”

What the sources say

• Not checked yetcites [84] Zweier JL Wang P Kuppusamy P Direct measurement of nitric oxide generation in the ischemic heart using electron paramagnetic resonance spectroscopy The Journal of biological chemistry 270 304 307 1995 7814391 source
• Not checked yetcites [85] Benjamin N Vallance P Plasma nitrite as a marker of nitric oxide production Lancet 344 960 1994 7934376 source
• Not checked yetcites [86] Lundberg JO Hellstrom PM Lundberg JM Alving K Greatly increased luminal nitric oxide in ulcerative colitis Lancet 344 1673 1674 1994 7996962 source

In the paper

“Moreover, a study by Zhang et al indicates that XO enzyme inactivation can result from XO-induced NO production involving nitrite reduction [90].”

What the sources say

• Not checked yetcites [90] Zhang Z Naughton D Winyard PG Benjamin N Blake DR Symons MC Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity Biochem Biophys Res Commun 249 767 772 1998 9731211 source

In the paper

“Importantly, all of these pathways serve to maintain adequate NO levels independent of typical NO generation through a L-arginine/NOS pathway.”

In the paper

“Oxygenated hemoglobin is an extremely effective NO scavenger that reacts rapidly with NO to form nitrate and methemoglobin (met-Hb) [105].”

What the sources say

• Not checked yetcites [105] Joschi MS FTJ Han TH Hyduke DR Liao JC Rassaf T Bryan N Feelisch M Lancaster JR Jr Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions Proceedings of the National Academy of Sciences of the United States of America 99 10341 10346 2002 12124398 PMC124916 source

In the paper

“Moreover, xanthine or hypoxanthine was found to inhibit this reaction [101].”

What the sources say

• Not checked yetcites [101] Millar TM Stevens CR Benjamin N Eisenthal R Harrison R Blake DR Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions FEBS Lett 427 225 228 1998 9607316 source

In the paper

“Different groups have shown that NADH can act as an electron donor to XO to catalyze nitrite reduction [90, 101].”

What the sources say

• Not checked yetcites [90] Zhang Z Naughton D Winyard PG Benjamin N Blake DR Symons MC Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity Biochem Biophys Res Commun 249 767 772 1998 9731211 source
• Not checked yetcites [101] Millar TM Stevens CR Benjamin N Eisenthal R Harrison R Blake DR Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions FEBS Lett 427 225 228 1998 9607316 source

In the paper

“However, XO may also catalytically reduce nitrite back to NO under several circumstances [90, 100, 101].”

What the sources say

• Not checked yetcites [90] Zhang Z Naughton D Winyard PG Benjamin N Blake DR Symons MC Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity Biochem Biophys Res Commun 249 767 772 1998 9731211 source
• Not checked yetcites [100] Godber BL Doel JJ Sapkota GP Blake DR Stevens CR Eisenthal R Harrison R Reduction of nitrite to nitric oxide catalyzed by xanthine oxidoreductase The Journal of biological chemistry 275 7757 7763 2000 10713088 source
• Not checked yetcites [101] Millar TM Stevens CR Benjamin N Eisenthal R Harrison R Blake DR Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions FEBS Lett 427 225 228 1998 9607316 source

In the paper

“At physiological pH (7.0–7.4), nitrite anions are fairly stable in the absence of compounds like oxyhemoglobin.”

In the paper

“Though acidic reduction is a well known pathway for nitrite reduction to NO, the amount of NO generated in this way is dependent not only on pH and nitrite concentrations but also on the presence of other reducing agents, proximity to heme groups, thiols, proteins and oxygen concentration [98].”

What the sources say

• Not checked yetcites [98] Weitzberg E Lundberg JO Nonenzymatic nitric oxide production in humans Nitric Oxide 2 1 7 1998 9706737 source

In the paper

“Heme dependent nitrite reduction to NO can be accomplished through different globin proteins including deoxyhemoglobin, deoxymyoglobin, neuroglobin, and cytoglobin [19, 87].”

What the sources say

• Not checked yetcites [19] Cosby K Partovi KS Crawford JH Patel RP Reiter CD Martyr S Yang BK Waclawiw MA Zalos G Xu X Huang KT Shields H Kim-Shapiro DB Schechter AN Cannon RO 3rd Gladwin MT Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nature medicine 9 1498 1505 2003 14595407 source
• Not checked yetcites [87] Hunter CJ Dejam A Blood AB Shields H Kim-Shapiro DB Machado RF Tarekegn S Mulla N Hopper AO Schechter AN Power GG Gladwin MT Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator Nature medicine 10 1122 1127 2004 15361865 source

In the paper

“Moreover, mitochondria derived NO plays an important role as an antioxidant by reacting with potential harmful ROS.”

In the paper

“This was later confirmed by Kozlov’s group who illustrated that cytochrome c oxidase was an important regulator of nitrite reduction to NO in the mitochondria [120, 121].”

What the sources say

• Not checked yetcites [120] Kozlov A Staniek K Nohl H Nitrite reductase activity is a novel function of mammalian mitochondria FEBS Lett 454 127 130 1999 10413109 source
• Not checked yetcites [121] Nohl H Staniek K Sobhian B Bahrami S Redl H Kozlov AV Mitochondria recycle nitrite back to the bioregulator nitric monoxide Acta Biochim Pol 47 913 921 2000 11996114 source

In the paper

“Components of the mitochondrial respiratory chain are capable of reducing nitrite to NO due to their roles as carriers during electron transport.”

In the paper

“Numerous other nitrite reduction mechanisms have been identified besides those discussed above including: aldehyde dehydrogenase, carbonic anhydrase, and endothelial nitric oxide synthase [130–132].”

What the sources say

• Not checked yetcites [130] Aamand R Dalsgaard T Jensen FB Simonsen U Roepstorff A Fago A Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation American journal of physiology 297 H2068 2074 2009 19820197 source
• Not checked yetcites [131] Badejo AM Jr Hodnette C Dhaliwal JS Casey DB Pankey E Murthy SN Nossaman BD Hyman AL Kadowitz PJ Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat American journal of physiology 299 H819 826 2010 20543077 PMC2944483 source
• Not checked yetcites [132] Vanin AF Bevers LM Slama-Schwok A van Faassen EE Nitric oxide synthase reduces nitrite to NO under anoxia Cell Mol Life Sci 64 96 103 2007 17160351 PMC11136343 source

In the paper

“Moreover, recent reports also demonstrate that neuroglobin and cytoglobin may also facilitate nitrite reduction [39, 115].”

What the sources say

• Not checked yetcites [39] Shiva S HZ Grubina R Sun J Ringwood LA MacArthur PH Xu X Murphy E Darley-Usmar VM Gladwin MT Deoxymyoglobin is a nitrite reducatse that generates nitric oxide and regulates mitochondrial respiration Circulation research 100 654 661 2007 17293481 source
• Not checked yetcites [115] Petersen MG Dewilde S Fago A Reactions of ferrous neuroglobin and cytoglobin with nitrite under anaerobic conditions Journal of inorganic biochemistry 102 1777 1782 2008 18599123 source

In the paper

“NO metabolism in the mitochondria plays a key role in regulating cellular respiration, mitochondrial transmembrane potential and transmembrane pH gradient [35].”

What the sources say

• Not checked yetcites [35] Burwell LS Nadtochiy SM Brookes PS Cardioprotection by metabolic shut-down and gradual wake-up J Mol Cell Cardiol 46 804 810 2009 19285082 PMC2683198 source

In the paper

“Importantly, the reductase efficacy of these enzymes is directly related to oxygen tension typically requiring a large drop in tissue oxygen tension before acting as a nitrite reductase.”

In the paper

“These results again highlight that nitrite reduction back to NO serves as an alternative pathway to augment tissue NO levels.”

In the paper

“Nagababu et al also reported that deoxyhemoglobin mediated nitrite reduction to NO via chemiluminescent techniques coupled with EPR identifying chemical intermediates of the reaction [108].”

What the sources say

• Not checked yetcites [108] Nagababu E Ramasamy S Abernethy DR Rifkind JM Active nitrite oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction Journal of Biological Chemistry 278 46349 46356 2003 12952953 source

In the paper

“Recent work from several laboratories indicates that myoglobin serves as an important reductase during tissue ischemia [111, 112].”

What the sources say

• Not checked yetcites [111] McNulty PH Scott S Kehoe V Kozak M Sinoway LI Li J Nitrite consumption in ischemic rat heart catalyzed by distinct blood-borne and tissue factors American journal of physiology 295 H2143 2148 2008 18820031 PMC2654027
• Not checked yetcites [112] Ormerod JO Ashrafian H Maher AR Arif S Steeples V Born GV Egginton S Feelisch M Watkins H Frenneaux MP The role of vascular myoglobin in nitrite-mediated blood vessel relaxation Cardiovascular research 89 560 565 2011 20889759 PMC3028970 source

In the paper

“Older in vitro studies with porcine skeletal muscle revealed that cytochrome c oxidase may catalyze nitrite reduction under anaerobic conditions [88, 116–118].”

What the sources say

• Not checked yetcites [88] Walters CL Taylor AM Pig-Heart Myoglobin and Its Derivatives with Nitric Oxide Biochimica et biophysica acta 82 420 422 1964 14127975 source
• Not checked yetcites [116] Burger IH Walters CL Interaction of nitrite with mammalian mitochondrial cytochromes The Biochemical journal 123 9P 1971 PMC1176952 4331372 source
• Not checked yetcites [117] Meyer DJ Enzymatic/non-enzymatic formation of nitric oxide Nature medicine 1 1103 1104 1995 7584968 source
• Not checked yetcites [118] Walters CL Taylor AM The Reduction of Nitrite by Skeletal-Muscle Mitochondria Biochimica et biophysica acta 96 522 524 1965 14314389 source

In the paper

“In these studies, genetic deletion of myoglobin in the heart significantly diminished the protective effect of sodium nitrite on myocardial ischemia-reperfusion [113, 114].”

What the sources say

• Not checked yetcites [113] Rassaf T Flogel U Drexhage C Hendgen-Cotta U Kelm M Schrader J Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of cardiac energetics and function Circulation research 100 1749 1754 2007 17495223 source
• Not checked yetcites [114] Hendgen-Cotta UB Merx MW Shiva S Schmitz J Becher S Klare JP Steinhoff HJ Goedecke A Schrader J Gladwin MT Kelm M Rassaf T Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury Proc Natl Acad Sci USA 105 10256 10261 2008 18632562 PMC2481313 source

In the paper

“While it has been well known that prokaryotes contain numerous nitrite/nitrate reductases, the confirmation that eukaryotic cells employ enzymatic nitrite reduction has only recently become clear [129].”

What the sources say

• Not checked yetcites [129] Cutruzzola F Rinaldo S Castiglione N Giardina G Pecht I Brunori M Nitrite reduction: a ubiquitous function from a pre-aerobic past Bioessays 31 885 891 2009 19554608 source

In the paper

“Most recently, Larsen et al demonstrated that dietary nitrate enhancement of muscle function during exercise involved increased muscle mitochondrial oxidative phosphorylation efficiency that is associated with reduced ATP/ADP translocase expression [128].”

What the sources say

• Not checked yetcites [128] Larsen FJ Schiffer TA Borniquel S Sahlin K Ekblom B Lundberg JO Weitzberg E Dietary inorganic nitrate improves mitochondrial efficiency in humans Cell Metab 13 149 159 2011 21284982 source

In the paper

“However, numerous other pathological conditions involving acute or chronic inflammation, neurological dysfunction, and cancer are also significantly affected by NO.”

In the paper

“Current therapeutic use of sodium nitrite is for the treatment of cyanide poisoning.”

In the paper

“Recent work from Basu and colleagues reported that liposomes containing cytochrome c also reduces nitrite to NO in a pH and nitrite concentration dependent manner [122].”

What the sources say

• Not checked yetcites [122] Basu S Azarova NA Font MD King SB Hogg N Gladwin MT Shiva S Kim-Shapiro DB Nitrite reductase activity of cytochrome c The Journal of biological chemistry 283 32590 32597 2008 18820338 PMC2583304 source

In the paper

“Several other studies extended the idea that nitrite therapy is protective against ischemia-reperfusion injury in different organs including the brain [157] and kidney (depending on route of administration) [158, 159].”

What the sources say

• Not checked yetcites [158] Basireddy M Isbell TS Teng X Patel RP Agarwal A Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney Am J Physiol Renal Physiol 290 F779 786 2006 16278276 source
• Not checked yetcites [159] Tripatara P Patel NS Webb A Rathod K Lecomte FM Mazzon E Cuzzocrea S Yaqoob MM Ahluwalia A Thiemermann C Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase J Am Soc Nephrol 18 570 580 2007 17202421 source

In the paper

“NO production of nitrite can also act in an endocrine manner to augment distal tissue function.”

In the paper

“Several other studies extended the idea that nitrite therapy is protective against ischemia-reperfusion injury in different organs including the brain [157] and kidney (depending on route of administration) [158, 159].”

What the sources say

• Not checked yetcites [157] Jung KH Chu K Ko SY Lee ST Sinn DI Park DK Kim JM Song EC Kim M Roh JK Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury Stroke 37 2744 2750 2006 17008610 source

In the paper

“Gonzalez et al demonstrated that even after 5 minutes of reperfusion nitrite therapy conferred myocardial cytoprotection [160].”

What the sources say

• Not checked yetcites [160] Gonzalez FM Shiva S Vincent PS Ringwood LA Hsu LY Hon YY Aletras AH Cannon RO 3rd Gladwin MT Arai AE Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction Circulation 117 2986 2994 2008 18519850 PMC2587279 source

In the paper

“This paper proved that near physiological doses of sodium nitrite (high nanomolar) were highly cytoprotective in both myocardial and hepatic ischemia-reperfusion extending previous work from Cosby et al demonstrating that near physiological levels of nitrite anion mediated hypoxic vasodilation responses [19].”

What the sources say

• Not checked yetcites [156] Duranski MR Greer JJ Dejam A Jaganmohan S Hogg N Langston W Patel RP Yet SF Wang X Kevil CG Gladwin MT Lefer DJ Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver The Journal of clinical investigation 115 1232 1240 2005 15841216 PMC1077170 source
• Not checked yetcites [19] Cosby K Partovi KS Crawford JH Patel RP Reiter CD Martyr S Yang BK Waclawiw MA Zalos G Xu X Huang KT Shields H Kim-Shapiro DB Schechter AN Cannon RO 3rd Gladwin MT Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nature medicine 9 1498 1505 2003 14595407 source

In the paper

“expanded understanding of nitrite as a hypoxia-dependent source of NO and signaling responses suggest that nitrite itself may be an important participant in physiological vasoregulation responses to tissue hypoxia.”

In the paper

“Together, these and other findings suggest that plasma and tissue levels of nitrite closely reflect NOS activity as well as NO metabolism that is associated with pathophysiological conditions.”

In the paper

“Lastly, it has also been reported that side effects such as mild methemoglobinemia (1–3%) may be observed with doses >2–3 mg/kg of sodium nitrite.”

In the paper

“Accumulating evidence demonstrates that nitrite anion acts as a physiological intermediary for several cellular responses known to involve nitric oxide.”

In the paper

“Human and animal studies of NO gas inhalation suggest that nitrite mediates many of the systemic therapeutic effects of inhaled NO, including peripheral vasodilation and prevention of ischemia-reperfusion-mediated tissue infarction [19, 109, 148, 151, 152].”

What the sources say

• Not checked yetcites [19] Cosby K Partovi KS Crawford JH Patel RP Reiter CD Martyr S Yang BK Waclawiw MA Zalos G Xu X Huang KT Shields H Kim-Shapiro DB Schechter AN Cannon RO 3rd Gladwin MT Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nature medicine 9 1498 1505 2003 14595407 source
• Not checked yetcites [109] Crawford JH Isbell TS Huang Z Shiva S Chacko BK Schechter AN Darley-Usmar VM Kerby JD Lang JD Jr Kraus D Ho C Gladwin MT Patel RP Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation Blood 107 566 574 2006 16195332 PMC1895612 source
• Not checked yetcites [148] Dejam A Hunter CJ Tremonti C Pluta RM Hon YY Grimes G Partovi K Pelletier MM Oldfield EH Cannon RO 3rd Schechter AN Gladwin MT Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation Circulation 116 1821 1831 2007 17893272 source

In the paper

“the authors demonstrated that sodium nitrite treatment of ischemic hearts ex vivo could generate NO upon treatment with 10–100 μM sodium nitrite.”

What the sources say

• Not checked yetcites [89] Webb A Bond R McLean P Uppal R Benjamin N Ahluwalia A Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage Proceedings of the National Academy of Sciences of the United States of America 101 13683 13688 2004 15347817 PMC518813 source

In the paper

“biochemical and physiological studies suggest that hemoglobin allosteric reduction of nitrite to NO along arterial to venous vasculature contributes to physiological hypoxic vasodilation [19, 87, 153].”

What the sources say

• Not checked yetcites [19] Cosby K Partovi KS Crawford JH Patel RP Reiter CD Martyr S Yang BK Waclawiw MA Zalos G Xu X Huang KT Shields H Kim-Shapiro DB Schechter AN Cannon RO 3rd Gladwin MT Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nature medicine 9 1498 1505 2003 14595407 source
• Not checked yetcites [87] Hunter CJ Dejam A Blood AB Shields H Kim-Shapiro DB Machado RF Tarekegn S Mulla N Hopper AO Schechter AN Power GG Gladwin MT Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator Nature medicine 10 1122 1127 2004 15361865 source
• Not checked yetcites [153] Maher AR Milsom AB Gunaruwan P Abozguia K Ahmed I Weaver RA Thomas P Ashrafian H Born GV James PE Frenneaux MP Hypoxic modulation of exogenous nitrite-induced vasodilation in humans Circulation 117 670 677 2008 18212289

In the paper

“Recent studies indicate that plasma and tissue levels of nitrite can serve as accurate indicators of NO generation.”

In the paper

“Sodium nitrite is very well absorbed with a bioavailability of > 98% in humans and rodents.”

What the sources say

• Not checked yetcites [69] Hunault CC van Velzen AG Sips AJ Schothorst RC Meulenbelt J Bioavailability of sodium nitrite from an aqueous solution in healthy adults Toxicology letters 190 48 53 2009 19576277 source

In the paper

“Lauer et al have shown that plasma concentrations of nitrite reflect acute changes in regional eNOS activity and NO bioavailability that are sensitive to pharmacological modulation of the L-arginine - NO pathway [147].”

What the sources say

• Not checked yetcites [147] Lauer T PM Rassaf T Strauer BE Deussen A Feelisch M Kelm M Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action Proceedings of the National Academy of Sciences of the United States of America 98 12814 12819 2001 11606734 PMC60136 source

In the paper

“Elrod et al documented significant increases in nitrite, nitrate, and nitrosothiols in the heart, plasma, and liver [164].”

What the sources say

• Not checked yetcites [164] Elrod JW Calvert JW Gundewar S Bryan NS Lefer DJ Nitric oxide promotes distant organ protection: evidence for an endocrine role of nitric oxide Proceedings of the National Academy of Sciences of the United States of America 105 11430 11435 2008 18685092 PMC2516252 source

In the paper

“The potent effect of low doses of nitrite on limiting ischemia-reperfusion infarction suggests that nitrite may modulate critical pathophysiological stress responses, particularly those involved during tissue ischemia [47, 161].”

What the sources say

• Not checked yetcites [47] Kumar D Branch BG Pattillo CB Hood J Thoma S Simpson S Illum S Arora N Chidlow JH Jr Langston W Teng X Lefer DJ Patel RP Kevil CG Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proceedings of the National Academy of Sciences of the United States of America 105 7540 7545 2008 18508974 PMC2396555 source
• Not checked yetcites [161] Kevil CG Lefer DJ Review focus on inorganic nitrite and nitrate in cardiovascular health and disease Cardiovascular research 89 489 491 2011 21183508 PMC3028981 source

In the paper

“Moreover, studies by the Kelm laboratory further revealed that plasma nitrite levels are inversely proportional to the number of cardiovascular risk factors and endothelial cell dysfunction [17, 80].”

What the sources say

• Not checked yetcites [17] Kleinbongard P Dejam A Lauer T Rassaf T Schindler A Picker O Scheeren T Godecke A Schrader J Schulz R Heusch G Schaub GA Bryan NS Feelisch M Kelm M Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals Free radical biology & medicine 35 790 796 2003 14583343 source
• Not checked yetcites [80] Heiss C Dejam A Kleinbongard P Schewe T Sies H Kelm M Vascular effects of cocoa rich in flavan-3-ols JAMA 290 1030 1031 2003 12941674 source

In the paper

“Importantly, continuous sodium nitrite administration in non-human primates was not associated with tolerance as is seen with organic nitrates [148].”

What the sources say

• Not checked yetcites [148] Dejam A Hunter CJ Tremonti C Pluta RM Hon YY Grimes G Partovi K Pelletier MM Oldfield EH Cannon RO 3rd Schechter AN Gladwin MT Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation Circulation 116 1821 1831 2007 17893272 source

In the paper

“cytoprotective effects were also examined using a myocardial ischemia-reperfusion model in dogs, further illustrating the therapeutic potential for this molecule [160].”

What the sources say

• Not checked yetcites [160] Gonzalez FM Shiva S Vincent PS Ringwood LA Hsu LY Hon YY Aletras AH Cannon RO 3rd Gladwin MT Arai AE Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction Circulation 117 2986 2994 2008 18519850 PMC2587279 source

In the paper

“The circulating half-life of nitrite is brief with an average between 25–35 minutes.”

What the sources say

• Not checked yetcites [69] Hunault CC van Velzen AG Sips AJ Schothorst RC Meulenbelt J Bioavailability of sodium nitrite from an aqueous solution in healthy adults Toxicology letters 190 48 53 2009 19576277 source

In the paper

“A separate study by Kleinbongard and colleagues reported that plasma nitrite levels reflect NOS activity in mammals [17].”

What the sources say

• Not checked yetcites [17] Kleinbongard P Dejam A Lauer T Rassaf T Schindler A Picker O Scheeren T Godecke A Schrader J Schulz R Heusch G Schaub GA Bryan NS Feelisch M Kelm M Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals Free radical biology & medicine 35 790 796 2003 14583343 source

In the paper

“The loss of nitrite vasodilation upon removal of the endothelial monolayer also implicated this cell compartment as an important source of nitrite reduction within the vasculature [154].”

What the sources say

• Not checked yetcites [154] Demoncheaux EA Higenbottam TW Foster PJ Borland CD Smith AP Marriott HM Bee D Akamine S Davies MB Circulating nitrite anions are a directly acting vasodilator and are donors for nitric oxide Clin Sci (Lond) 102 77 83 2002 11749663 source

In the paper

“sodium nitrite therapy could protect against ischemia induced pump dysfunction as nitrite therapy increased rat heart left ventricular developed pressure after ischemic insult.”

What the sources say

• Not checked yetcites [89] Webb A Bond R McLean P Uppal R Benjamin N Ahluwalia A Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage Proceedings of the National Academy of Sciences of the United States of America 101 13683 13688 2004 15347817 PMC518813 source

In the paper

“CS-eNOS-Tg mice displayed a significant protection against hepatic I/R injury due to the increase in hepatic NO metabolites originating from the myocardium.”

What the sources say

• Not checked yetcites [164] Elrod JW Calvert JW Gundewar S Bryan NS Lefer DJ Nitric oxide promotes distant organ protection: evidence for an endocrine role of nitric oxide Proceedings of the National Academy of Sciences of the United States of America 105 11430 11435 2008 18685092 PMC2516252 source

In the paper

“Duranski et al showed that nitrite therapy protects against ischemic tissue injury through a heme oxygenase-1 pathway which further implicated the generation of nitrite dependent NO during therapy.”

What the sources say

• Not checked yetcites [156] Duranski MR Greer JJ Dejam A Jaganmohan S Hogg N Langston W Patel RP Yet SF Wang X Kevil CG Gladwin MT Lefer DJ Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver The Journal of clinical investigation 115 1232 1240 2005 15841216 PMC1077170 source

In the paper

“Kenjale et al has also recently reported that dietary nitrate can enhance exercise performance in PAD patients thus it appears that nitrite therapy maybe clinically beneficial [175].”

What the sources say

• Not checked yetcites [175] Kenjale AA Ham KL Stabler T Robbins JL Johnson JL Vanbruggen M Privette G Yim E Kraus WE Allen JD Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease Free Radic Biol Med 3 21 [epub ahead of print] PMC3119136 21454745 source

In the paper

“A previous study from Lang et al demonstrated that inhaled NO therapy before liver transplanation significantly elevated tissue nitrite levels that were associated with cytoprotection [166].”

What the sources say

• Not checked yetcites [166] Lang JD Jr Teng X Chumley P Crawford JH Isbell TS Chacko BK Liu Y Jhala N Crowe DR Smith AB Cross RC Frenette L Kelley EE Wilhite DW Hall CR Page GP Fallon MB Bynon JS Eckhoff DE Patel RP Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation The Journal of clinical investigation 117 2583 2591 2007 17717604 PMC1950460 source

In the paper

“Li and colleagues reported that nitrite administration confers protection against liver cold ischemia-reperfusion injury [167].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [167] Li W Meng ZH Liu YL Reyes JD Lang JD The protective effect of Nitrite on Liver cold Ischemia reperfusion injury Liver Transplantation 15 S236 S236 2009

In the paper

“A recent study by Zuckerbraun et al reported that nebulized nitrite administered either once or three times a week significantly prevented or reversed hypoxia or monocrotaline induced pulmonary artery hypertension [197].”

What the sources say

• Not checked yetcites [197] Zuckerbraun BS Shiva S Ifedigbo E Mathier MA Mollen KP Rao J Bauer PM Choi JJ Curtis E Choi AM Gladwin MT Nitrite potently inhibits hypoxic and inflammatory pulmonary artery hypertension and smooth muscle proliferation via xanthine oxidoreductase-dependent nitric oxide generation Circulation 121 98 109 2010 20026772

In the paper

“Therefore, it is reasonable to predict that exogenous nitrite therapy may be beneficial for this disease.”

In the paper

“NO bioavailability also plays an important role modulating chronic tissue ischemia responses [168, 169].”

What the sources say

• Not checked yetcites [168] Hudlicka O Brown MD Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor Journal of vascular research 46 504 512 2009 19556804 source
• Not checked yetcites [169] Pignataro G Scorziello A Di Renzo G Annunziato L Post-ischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy The FEBS journal 276 46 57 2009 19087199 source

In the paper

“Their work nicely demonstrated that increasing plasma nitrite levels resulted in a marked reduction in blood pressure levels in normotensives”

What the sources say

• Not checked yetcites [191] Webb AJ Patel N Loukogeorgakis S Okorie M Aboud Z Misra S Rashid R Miall P Deanfield J Benjamin N MacAllister R Hobbs AJ Ahluwalia A Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite Hypertension 51 784 790 2008 18250365 PMC2839282 source

In the paper

“Recent work from Allen et al indicates that plasma nitrite levels may be an important indicator of vascular health and function in PAD patients.”

In the paper

“induction of plasma nitrite levels during supervised exercise therapy were significantly blunted in diabetic patients with PAD versus non-diabetic PAD patients or diabetics alone [173].”

What the sources say

• Not checked yetcites [173] Allen JD Miller EM Schwark E Robbins JL Duscha BD Annex BH Plasma nitrite response and arterial reactivity differentiate vascular health and performance Nitric Oxide 20 231 237 2009 19371597 PMC2676216 source

In the paper

“the authors found that plasma nitrite flux predicted the time to claudication onset pain reflecting exercise performance ability [174].”

What the sources say

• Not checked yetcites [174] Allen JD Stabler T Kenjale A Ham KL Robbins JL Duscha BD Dobrosielski DA Annex BH Plasma nitrite flux predicts exercise performance in peripheral arterial disease after 3 months of exercise training Free radical biology & medicine 49 1138 1144 2010 20620208 PMC2922965 source

In the paper

“Together, these studies indicate that sodium nitrite may be useful in preventing transplantation ischemia-reperfusion injury; however, additional investigation in this area is certainly needed.”

In the paper

“In a study by Rodriguez et al it was reported that administration of bolus nitrite (30–100 nmol) at the onset of hemoglobin based oxygen carriers (HBOC-201) resuscitation prevented hypertension [198].”

What the sources say

• Not checked yetcites [198] Rodriguez C Vitturi DA He J Vandromme M Brandon A Hutchings A Rue LW Kerby JD Patel RP Sodium nitrite therapy attenuates the hypertensive effects of HBOC-201 via nitrite reduction Biochem J 422 423 432 2009 19555351 PMC2775055 source