The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Open accessAbstract
Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action of xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by deoxyhemoglobin, myoglobin, and tissue heme proteins. Because the rate of NO generation from nitrite is linearly dependent on reductions in oxygen and pH levels, we hypothesized that nitrite would be reduced to NO in ischemic tissue and exert NO-dependent protective effects. Solutions of sodium nitrite were administered in the setting of hepatic and cardiac ischemia-reperfusion (I/R) injury in mice. In hepatic I/R, nitrite exerted profound dose-dependent protective effects on cellular necrosis and apoptosis, with highly significant protective effects observed at near-physiological nitrite concentrations. In myocardial I/R injury, nitrite reduced cardiac infarct size by 67%. Consistent with hypoxia-dependent nitrite bioactivation, nitrite was reduced to NO, S-nitrosothiols, N-nitros-amines, and iron-nitrosylated heme proteins within 1-30 minutes of reperfusion. Nitrite-mediated protection of both the liver and the heart was dependent on NO generation and independent of eNOS and heme oxygenase-1 enzyme activities. These results suggest that nitrite is a biological storage reserve of NO subserving a critical function in tissue protection from ischemic injury. These studies reveal an unexpected and novel therapy for diseases such as myocardial infarction, organ preservation and transplantation, and shock states.
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In the citing paper
“Furthermore, the process was demonstrated to be dependent on xanthine oxidoreductase (XOR)”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [160]
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Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Early research indicated a therapeutic role for nitric oxide in cardioprotection in myocardial infarction models, 135 and L-arginine treatment before reperfusion was also organ-protective.133,136,137”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [135]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Pre-clinical studies with nitrate or nitrite also show the potential to protect against ischaemia-reperfusion injury and reduce arterial stiffness, inflammation and intimal thickness.”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [160]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Chronic inhibition of XOR with allopurinol or 3 weeks of tungstenrich diet increased intimal hyperplasia.”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [160]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Even the late introduction of nitrite was able to reverse intimal hyperplasia [160].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [160]
Experimental — accuracy not yet measured
In the citing paper
“The nitrite (NO2−) anion protects from ischemia-reperfusion injury in vivo1–3,37 and is thought to act as an S-nitrosating agent in the ischemic myocardium2.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [1]
In the citing paper
“Nitrite is a dietary constituent that protects the heart against I/R injury in many animal models during both ischemia and preconditioning stage [186,187,188,189,190,191,192].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [186]
In the citing paper
“while nitrate supplementation prevents or limits ischemia-reperfusion injury and endothelial dysfunction in both animal[98,120–124] and human[97,125] models of ischemia-reperfusion.”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [121]
In the citing paper
“the nitrate/nitrite content of the fruits and vegetables could contribute to their cardiovascular health benefits in animals [29,33,78,79,80,81,82,83] and humans [31,84,85,86].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [79]
In the citing paper
“Physiologically relevant levels of nitrite have been shown to counter ischemic-reperfusion injury [8–10]”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [9]
In the citing paper
“The efficacy of low concentrations of nitrite in mediating cytoprotection has been demonstrated in a variety of tissues in animal models including heart [8, 9, 55, 118–122] liver [9, 120, 123], brain [124–126], kidney [127, 128], hindlimb [129], and human forearm [23].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [9]
In the citing paper
“pretreatment with this compound, delivered as a salt in the form of sodium nitrite, protects against ischemia/reperfusion (I/R) injury in the heart in preclinical models (7, 19, 20, 40, 46, 60, 79, 189).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [46]
In the citing paper
“nitrite administration reduces skeletal muscle (188), renal (125, 179), and liver (46, 154, 169) injury after ischemia.”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [46]
In the citing paper
“exogenous administration of nitrite correlates with increased levels of S-nitrosothiols in red blood cells and other tissues both in vivo and in vitro [25, 43, 46-53].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing paper
“Evidence for a role for NO is dependent largely on attenuation of responses by the NO-scavenger CPTIO [25, 26, 52, 100] and measurement of nitrite-dependent increases in cGMP levels[26, 101].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing paper
“Murine based studies of hepatic and myocardial IR injury have shown a ‘U’ shaped profile for nitrite effects; namely protection increases with increasing dose up to a point and then as the dose is increased further, protection is lost and can -if even higher doses are administered, exacerbate injury [52, 114].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing paper
“nitration reactions could also explain the loss of protection observed when higher doses of nitrite are administered in the context of IR injury [52, 114].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing paper
“the nitrite dose range encompassing protection versus loss of protection in these studies was greater than two or three orders of magnitude.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing paper
“experimental observations show that relatively low doses of nitrite are sufficient to induce dramatic protective effects in vivo.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing paper
“Typically doses of ~50 nmoles have been shown to be protective in models of ischemia reperfusion [52, 114] as well hemorrhagic shock in mice [122] for example.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [52]
In the citing 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.”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [156]
In the citing paper
“cPTIO treatment was shown by numerous groups to attenuate nitrite mediated protection against ischemia-reperfusion injury in vivo indicating that protective mechanisms likely involve NO dependent signaling pathways and molecular responses [47, 89, 156, 162].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [156]
In the citing 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].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [156]
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Citations
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Self-citationEffects of sodium nitrite on ischemia–reperfusion injury in the rat kidney
Basireddy, M., Isbell, T. S., Teng, X., Patel, R. P., & Agarwal, A. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00334.2005 · Cited by 72
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BackgroundMethodResultInfluentialSelf-citationA Review of the Pathophysiology and Novel Treatments for Erectile Dysfunction
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“[98] M.”
BackgroundNitrite, a naturally occurring precursor of nitric oxide that acts like a ‘prodrug’
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“Application of near-physiological nitrite concentrations has been found to lead to NO-dependent cytoprotection from cardiac and liver ischemia-reperfusion injury in mice (Webb et al., 2004; Duranski et al., 2005).”
BackgroundInfluentialPalevski, D., Levin‐Kotler, L., Kain, D., Naftali‐Shani, N., Landa, N., Ben‐Mordechai, T., Konfino, T., Holbová, R., Molotski, N., Rosin‐Arbesfeld, R., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.004387 · Cited by 76
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“showed a large effect in decrease of the infarct size when nitrite was applied during ischemia (23).”
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“An intraventricular injection of NaNO 2 given immediately before reperfusion protected against injury in rats (37), but most animal models have demonstrated bene fi t when NaNO 2 was injected before ischemia (38 – 40).”
Nitrite and nitric oxide metabolism in peripheral artery disease
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Self-citationNitrite and nitrate: cardiovascular risk–benefit and metabolic effect
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“Much of the initial work on the cardiovascular effects of nitrite shows that pretreatment with this compound, delivered as a salt in the form of sodium nitrite, protects against ischemia/reperfusion (I/R) injury in the heart in preclinical models (7, 19, 20, 40, 46, 60, 79, 189).”
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“Nitrite has been reported to represent both circulating and tissue storage forms of NO, which are activated during ischemia by oxidation of NO (43).”
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“It is particularly potent in the heart, where an increase in plasma nitrite concentration of just 200nM decreases infarct size by 50% in a murine model of myocardial infarction [11].”
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“Nitrite-mediated protection of the liver was dependent on NO generation and independent of endothelial NO synthase and heme oxygenase-1 enzyme activities (Duranski et al., 2005).”
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“It has been reported that sodium nitrite and acidified sodium nitrite have organ-protective effects in several ischemia-reperfusion injury models (10, 20, 21).”
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“Through NO release, oxygen may be conserved by controlling oxidative phosphorylation34 and by modifying HIF-1a.4,19,20,35,36 The same mechanism could also restore tissue oxygenation through vasodilatation.2”
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“…shown by a number of research groups that nitrite-derived bioactivity is cardioprotective by minimising cell death by apoptosis (Webb et al., 2004; Duranski et al., 2005; Dezfulian et al., 2007; Shiva et al., 2007a, 2007b; Tripatara et al., 2007), exerts anti-aggregatory effects (Srihirun et al.,…”
Minneci, P. C., Deans, K. J., Shiva, S., Zhi, H., Banks, S. M., Kern, S. J., Natanson, C., Solomon, S. B., & Gladwin, M. T. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00151.2008 · Cited by 62
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“Evidence for a role for NO is dependent largely on attenuation of responses by the NO scavenger CPTIO [25,26,52,100] and measurement of nitrite-dependent increases in cGMP levels [26,101].”
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Programmed death as a therapeutic target to reduce myocardial infarction
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“I/R is characterized by the formation of reactive oxygen species (ROS) on reintroduction of molecular oxygen to ischemic tissues, and this phenomenon (the sudden reintroduction of blood into ischemic tissue) results in massive tissue disruption, widespread lipid and protein oxidative modifications, enzymes release, re…”
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Murillo, D., Kamga, C., Mo, L., & Shiva, S. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.01.003 · Cited by 57
“In addition to these studies in which NO formation was directly measured, a number of the focal IR studies mentioned above have utilized the NO scavenger 2-(4carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (PTIO) [52-53,71,73].”
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Keeping the heart in balance: the functional interactions of myoglobin with nitrogen oxides
Flögel, U., Fago, A., & Rassaf, T. (2010) · Journal of Experimental Biology · doi:10.1242/jeb.041681 · Cited by 57
“…NO that can be activated along the physiological O2 gradient to mediate a number of important responses, including hypoxic vasodilation (Cosby et al., 2003), cytoprotection during ischemia/reperfusion (Duranski et al., 2005), as well as NO-dependent and independent signaling (Bryan et al., 2005).”
BackgroundSandvik, G. K., Nilsson, G., & Jensen, F. B. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00538.2011 · Cited by 57
“Like for the heart, nitrite has been found to protect brain (44), kidney (76), and liver (21, 64) tissue against ischemiareperfusion injury in mammals.”
BackgroundNitrite-Nitric Oxide Signaling and Cardioprotection
Totzeck, M., Hendgen-Cotta, U. B., & Rassaf, T. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55330-6_18 · Cited by 57
Gill, A., Zajda, J., & Meyerhoff, M. E. (2019) · Analytica Chimica Acta · doi:10.1016/j.aca.2019.05.065 · Cited by 57
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Self-citationMaia, L. B., & Moura, J. J. G. (2018) · Redox Biology · doi:10.1016/j.redox.2018.08.020 · Cited by 57
Cysteine Oxidations in Mitochondrial Membrane Proteins: The Case of VDAC Isoforms in Mammals
Reina, S., Pittalà, M. G. G., Guarino, F., Messina, A. A., Pinto, V. D., Foti, S., & Saletti, R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00397 · Cited by 58
Perlman, D. H., Bauer, S. M., Ashrafian, H., Bryan, N. S., Garcia-Saura, M. F., Lim, C. C., Fernandez, B. O., Infusini, G., McComb, M. E., Costello, C. E., et al. (2009) · Circulation Research · doi:10.1161/circresaha.108.187005 · Cited by 57
Peroxynitrite and myocardial contractility: In vivo versus in vitro effects
Katori, T., Donzelli, S., Tocchetti, C. G., Miranda, K. M., Cormaci, G., Thomas, D. D., Ketner, E., Lee, M. J., Mancardi, D., Wink, D. A., et al. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.023 · Cited by 56
Polhemus, D. J., Gao, J., Scarborough, A. L., Trivedi, R. K., McDonough, K. H., Goodchild, T. T., Smart, F. W., Kapusta, D. R., & Lefer, D. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.308278 · Cited by 53
Self-citationNitrite therapy is neuroprotective and safe in cardiac arrest survivors
Dezfulian, C., Alekseyenko, A., Dave, K. R., Raval, A. P., Do, R., Kim, F., & Pérez‐Pinzón, M. A. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.007 · Cited by 51
“8 lmol/kg) and the blood levels produced more closely approximated the ‘‘optimal’’ dose based on prior observations in focal heart, liver and brain ischemia-reperfusion [12].”
BackgroundMethodInfluentialMikula, I., Durocher, S., Martasek, P., Mutus, B., & Slama-Schwok, A. (2009) · Biochemical Journal · doi:10.1042/bj20080987 · Cited by 51
“In addition, nitrite has been shown to have protective, hypoxic buffer effects, under conditions of low oxygen tension [7-9].”
BackgroundIbrahim, Y., Ninnis, J. R., Hopper, A. O., Deming, D. D., Zhang, A. X., Herring, J. L., Sowers, L. C., McMahon, T., Power, G. G., & Blood, A. B. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2011.07.040 · Cited by 52
“may be converted directly to SNO-Hb by reaction with hemoglobin [25, 26].”
BackgroundCox, G., & Gillis, T. E. (2020) · Journal of Experimental Biology · doi:10.1242/jeb.207613 · Cited by 54
Abu‐Amara, M., Yang, S. Y., Quaglia, A., Rowley, P., Tapuria, N., Seifalian, A. M., Fuller, B. J., & Davidson, B. R. (2011) · Liver Transplantation · doi:10.1002/lt.22204 · Cited by 51
Cardioprotective effects of nitrite during exercise
Calvert, J. W. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq307 · Cited by 51
“However, it has been shown that nitrite-mediated protection is independent of eNOS and dependent on NO generation.(70) Nitrite can”
BackgroundUnderbakke, E. S., Sürmeli, N. B., Smith, B. C., Wynia‐Smith, S. L., & Marletta, M. A. (2013) · Elsevier eBooks · doi:10.1016/b978-0-08-097774-4.00320-x · Cited by 51
Grubina, R., Basu, S., Tiso, M., Kim‐Shapiro, D. B., & Gladwin, M. T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705222200 · Cited by 50
Self-citationMitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite
Yadav, A. K., Doran, S. F., Samal, A. A., Sharma, R., Vedagiri, K., Postlethwait, E. M., Squadrito, G. L., Fanucchi, M. V., Roberts, L. J., Patel, R. P., et al. (2010) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00278.2010 · Cited by 50
“NO2 -mediated protection against inflammatory tissue injury is thought to occur primarily by its reduction to NO by reduced hemoglobin in hypoxic red blood cells, which in turn could affect ALI by several mechanisms, including modulation of leukocyte adhesion and infiltration, inhibition of endothelial/ epithelial cel…”
BackgroundSelf-citationFrérart, F., Sonveaux, P., Rath, G., Smoos, A., Meqor, A., Charlier, N., Jordan, B. F., Saliez, J., Noël, A., Dessy, C., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4001 · Cited by 49
Martín, C., Schulz, R., Post, H., Boengler, K., Kelm, M., Kleinbongard, P., Gres, P., Skyschally, A., Konietzka, I., & Heusch, G. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.12.020 · Cited by 48
“Recently, nitrite has been reported to represent a circulating and tissue storage form of NO which is activated during ischemia, probably through the reduction of nitrite by desoxymyoglobin, desoxyhemoglobin, and/or other heme proteins [20].”
BackgroundKypreos, K. E., Zafirovic, S. S., Πετροπούλου, Π.-Ι., Bjelogrlic, P., Resanović, I., TRAISH, A. M., & Isenović, E. R. (2014) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248413513499 · Cited by 49
Augmentation of nitrite therapy in cerebral ischemia by NMDA receptor inhibition
Jung, K., Chu, K., Lee, S., Park, H.-K., Kim, J.-H., Kang, K., Kim, M., Lee, S. K., & Roh, J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.081 · Cited by 48
Dietary intake and bio-activation of nitrite and nitrate in newborn infants
Jones, J. A., Hopper, A. O., Power, G. G., & Blood, A. B. (2014) · Pediatric Research · doi:10.1038/pr.2014.168 · Cited by 50
“Although the resulting nitrite concentrations reached only ~300 nmol/l after iNO administration, similar increases in circulating nitrite concentrations have been shown to protect mice against hepatic infarct (71), increase blood flow in the human forearm (72), and decrease systolic blood pressure in adults (5,18,73).”
Zahran, Z. N., Chooback, L., Copeland, D. M., West, A. H., & Richter-Addo, G. B. (2007) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2007.08.002 · Cited by 47
Red blood cells in the metabolism of nitric oxide‐derived peroxynitrite
Romero, N., Denicola, A., & Radí, R. (2006) · IUBMB Life · doi:10.1080/15216540600936549 · Cited by 49
Dietary inorganic nitrate alleviates doxorubicin cardiotoxicity: Mechanisms and implications
Xi, L., Zhu, S., Das, A., Chen, Q., Durrant, D., Hobbs, D. C., Lesnefsky, E. J., & Kukreja, R. C. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.006 · Cited by 47
Nitric Oxide Donor Agents for the Treatment of Ischemia/Reperfusion Injury in Human Subjects
Roberts, B. W., Mitchell, J., Kilgannon, J. H., Chansky, M. E., & Trzeciak, S. (2013) · Shock · doi:10.1097/shk.0b013e31827f565b · Cited by 47
“In additional animal models of I/R injury, NO-donor agent administration was demonstrated to decrease infarction size and improve left ventricular function (11, 19Y22, 25), decrease hepatocellular necrosis and apoptosis (11, 21, 23), and attenuate renal injury (24).”
BackgroundOxygen Regulates Tissue Nitrite Metabolism
Curtis, E., Hsu, L. L., Noguchi, A. C., Geary, L., & Shiva, S. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4242 · Cited by 46
“Perhaps the most robust nitritedependent tissue response is the prevention of ischemia/ reperfusion (I/R) injury in the heart (16, 19, 23, 50), liver (19, 47), and brain (32).”
BackgroundHendgen-Cotta, U. B., Kelm, M., & Rassaf, T. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.10.003 · Cited by 46
Regulation of mammalian cellular metabolism by endogenous cyanide production
Zuhra, K., Petrosino, M., Janickova, L., Petrić, J., Ascenção, K., Vignane, T., Khalaf, M. M. R., Philipp, T. M., Ravani, S., Anand, A., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01225-w · Cited by 46
“7h); similar bell-shaped concentration–response effects have been previously observed for NO or H 2 S in this model 45,46 .”
Non-enzymatic NO production in human skin: Effect of UVA on cutaneous NO stores
Suschek, C. V., Opländer, C., & van Faassen, E. E. (2009) · Nitric Oxide · doi:10.1016/j.niox.2009.10.006 · Cited by 44
Shiva, S., Rassaf, T., Patel, R. P., & Gladwin, M. T. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq327 · Cited by 48
Self-citationNitrite and myocardial ischaemia reperfusion injury. Where are we now?
Griffiths, K., Lee, J. J., Frenneaux, M. P., Feelisch, M., & Madhani, M. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107819 · Cited by 46
Analysis of Nitric Oxide (NO) in Cerebral Vasospasm After Aneursymal Bleeding
Pluta, R. M., & Oldfield, E. H. (2007) · Reviews on Recent Clinical Trials · doi:10.2174/157488707779318062 · Cited by 46
Bouhidel, J. O., Wang, P., Siu, K. L., Li, H., Youn, J. Y., & Cai, H. “. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.06.005 · Cited by 44
Enhanced xanthine oxidoreductase expression and tissue nitrate reduction in germ free mice
Huang, L., Borniquel, S., & Lundberg, J. O. (2010) · Nitric Oxide · doi:10.1016/j.niox.2010.01.004 · Cited by 45
Yang, S. C., Wo, Y., & Meyerhoff, M. E. (2014) · Analytica Chimica Acta · doi:10.1016/j.aca.2014.06.041 · Cited by 44
Mohler, E. R., Hiatt, W. R., Gornik, H. L., Kevil, C. G., Quyyumi, A. A., Haynes, W. G., & Annex, B. H. (2013) · Vascular Medicine · doi:10.1177/1358863x13515043 · Cited by 43
Self-citationDonnarumma, E., Bhushan, S., Bradley, J., Otsuka, H., Donnelly, E. L., Lefer, D. J., & Islam, K. N. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003551 · Cited by 42
Self-citationSantharaman, P., Venkatesh, K. A., Kanagavel, V., Benjamin, A. R., Sethy, N. K., Bhargava, K., & Karunakaran, C. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.10.039 · Cited by 44
Single-Dose Pharmacokinetics of Different Oral Sodium Nitrite Formulations in Diabetes Patients
Greenway, F. L., Predmore, B. L., Flanagan, D. R., Giordano, T., Qiu, Y., Brandon, A., Lefer, D. J., Patel, R. P., & Kevil, C. G. (2012) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2011.0291 · Cited by 43
“Reports in patients and animal models reveal that increases in plasma nitrite levels in the low micromolar range (1–10 lM) elicit various responses such as vasodilation and tissue cytoprotection during acute ischemia/reperfusion injury.(18,21,22) Likewise, low plasma nitrite concentrations also stimulate angiogenic ac…”
Self-citationGowthaman, N. S. K., Amalraj, M., Kesavan, S., Rajalakshmi, K., Shankar, S., Sinduja, B., Arul, P., Karthikeyan, R., Loganathan, C., Gowri, V. M., et al. (2023) · Microchemical Journal · doi:10.1016/j.microc.2023.109291 · Cited by 43
Pattillo, C. B., Bir, S. C., Rajaram, V., & Kevil, C. G. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq297 · Cited by 44
“This process is important for nitrite-mediated cytoprotection during ischaemia that could involve different protective mechanisms.(45,58) Tissue ischaemia also increases molybdenum hydroxylase enzyme expression or activity which could also be important for nitrite reduction.”
BackgroundInfluentialSelf-citationThe biological role of nitrate and nitrite: The times they are a-changin’
Lundberg, J. O., & Weitzberg, E. (2009) · Nitric Oxide · doi:10.1016/j.niox.2009.11.004 · Cited by 44
A “green” diet-based approach to cardiovascular health? Is inorganic nitrate the answer?
Rathod, K. S., Velmurugan, S., & Ahluwalia, A. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500313 · Cited by 42
Lim, C. C., Bryan, N. S., Jain, M., Garcia-Saura, M. F., Fernandez, B. O., Sawyer, D. B., Handy, D. E., Loscalzo, J., Feelisch, M., & Liao, R. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00673.2009 · Cited by 44
Golwala, N. H., Hodenette, C., Murthy, S. N., Nossaman, B. D., & Kadowitz, P. J. (2009) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y09-101 · Cited by 41
“Although it was believed that nitrite is the physiological end product of NO oxidation, there is increasing evidence that nitrite may act as a recyclable storage form of vasoactive NO (Duranski et al. 2005; Jung et al. 2006; Lefer 2006).”
BackgroundNanomedicine‐Based Therapeutics for Myocardial Ischemic/Reperfusion Injury
Li, X., Ou, W., Xie, M., Yang, J., Li, Q., & Li, T. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202300161 · Cited by 40
Nitrite Reduces Acute Lung Injury and Improves Survival in a Rat Lung Transplantation Model
Sugimoto, R., Okamoto, T., Nakao, A., Zhan, J., Wang, Y., Kohmoto, J., Tokita, D., Farver, C. F., Tarpey, M. M., Billiar, T. R., et al. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04169.x · Cited by 40
Self-citationMabeku, L. B. K., Nana, B. N., Bille, B. E., Tchuenguem, R. T., & Nguepi, E. Z. (2017) · Pharmaceutical Biology · doi:10.1080/13880209.2017.1285326 · Cited by 41
“…since NO is known to play a role in maintaining gastric integrity by increasing mucosal blood flow and mucus secretion (Bjorne et al. 2004), cytoprotection (Duranski et al. 2005; Shiva et al. 2007) as well as anti-inflammatory and antioxidant effects (Stokes et al. 2009; Carlstrom et al. 2011).”
BackgroundThe eNOS enhancer AVE 9488: a novel cardioprotectant against ischemia reperfusion injury
Frantz, S., Adamek, A., Fraccarollo, D., Tillmanns, J., Widder, J. D., Dienesch, C., Schäfer, A., Podolskaya, A. A., Held, M. C., Ruetten, H., et al. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0041-3 · Cited by 41
“Nitrite treated mouse hearts exhibited profound reductions of infarct size after reperfusion [6].”
BackgroundTargeting the mitochondria to augment myocardial protection
SCHWARTZ, D., & Sack, M. N. (2008) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.12.008 · Cited by 41
“Indeed, administration of nitrite in preclinical studies confers protection against ischemia-reperfusion injury [59] in parallel with a reduction in post ischemic reactive oxygen species production and by reducing the activation of the MPTP [57].”
BackgroundLang, J. D., Smith, A. B., Brandon, A. P., Bradley, K. M., Liu, Y., Li, W., Crowe, D. R., Jhala, N. C., Cross, R. C., Frenette, L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086053 · Cited by 40
“ferrous-nitrosylhemoglobin (HbNO) and C- or N-nitrosamines (referred to as XNO) [34,37,38,39].”
BackgroundInfluentialSelf-citationHendgen-Cotta, U. B., Grau, M., Rassaf, T., Gharini, P. P. R., Kelm, M., & Kleinbongard, P. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)01216-0 · Cited by 40
Organ preservation in pancreas and islet transplantation
Baertschiger, R. M., Berney, T., & Morel, P. (2008) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e3282f44a63 · Cited by 39
Malek, M., & Nematbakhsh, M. (2014) · Advances in Preventive Medicine · doi:10.1155/2014/740647 · Cited by 40
Metadata
- Authors
- Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., Gladwin, M. T., & Lefer, D. J.
- Affiliations
- Louisiana State University Health Sciences Center Shreveport (US)
- Medical College of Wisconsin (US)
- University of Alabama at Birmingham (US)
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2005-04-14
- Volume
- 115
- Issue
- 5
- Pages
- 1232-1240
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1077170
- OpenAlex
- W2098453482
- Cited by
- 674
- References
- 70
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 9 · 2023: 7 · 2022: 21 · 2021: 22 · 2020: 20 · 2019: 18 · 2018: 23 · 2017: 40 · 2016: 31 · 2015: 45 · 2014: 42 · 2013: 42 · 2012: 59
- FWCI
- 28.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (2R01-HL60849, R01HL060849)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01-1 DK-43785, P01DK043785)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- nitrite, nitric oxide, ischemia-reperfusion injury, cardioprotection, hepatoprotection, sodium nitrite, S-nitrosothiols, nitrosamines, liver necrosis, apoptosis, organ preservation, myocardial infarction
- MeSH terms
- Animals, Heme Oxygenase (Decyclizing), Liver, Membrane Proteins, Mice, Inbred C57BL, Myocardium, Nitrites, Peritoneum, Reperfusion Injury, Nitric Oxide Synthase, Mice, Heme Oxygenase-1
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