Nitrite signaling in pulmonary hypertension: mechanisms of bioactivation, signaling, and therapeutics
Open accessAbstract
SIGNIFICANCE: Pulmonary arterial hypertension (PAH) is a disorder characterized by increased pulmonary vascular resistance and mean pulmonary artery pressure leading to impaired function of the right ventricle, reduced cardiac output, and death. An imbalance between vasoconstrictors and vasodilators plays an important role in the pathobiology of PAH. RECENT ADVANCES: Nitric oxide (NO) is a potent vasodilator in the lung, whose bioavailability and signaling pathway are impaired in PAH. It is now appreciated that the oxidative product of NO metabolism, the inorganic anion nitrite (NO(2)(-)), functions as an intravascular endocrine reservoir of NO bioactivity that can be reduced back to NO under physiological and pathological hypoxia. CRITICAL ISSUES: The conversion of nitrite to NO is controlled by coupled electron and proton transfer reactions between heme- and molybdenum-containing proteins, such as hemoglobin and xanthine oxidase, and by simple protonation and disproportionation, and possibly by catalyzed disproportionation. The two major sources of nitrite (and nitrate) are the endogenous L-arginine-NO pathway, by oxidation of NO, and the diet, with conversion of nitrate from diet into nitrite by oral commensal bacteria. In the current article, we review the enzymatic formation of nitrite and the available data regarding its use as a therapy for PAH and other cardiovascular diseases. FUTURE DIRECTIONS: The successful efficacy demonstrated in several animal models and safety in early clinical trials suggest that nitrite may represent a promising new therapy for PAH.
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Inorganic nitrite demonstrates robust NO-signaling effects and contributes to basal vascular tone, blood pressure, protection from endothelial dysfunction and vascular inflammation under conditions of metabolic and inflammatory stress.
“As with NOS-derived NO, inorganic nitrite demonstrates robust NO-signaling effects[52,53,57,59] and contributes to basal vascular tone[51,55,60,61], blood pressure[62–66], protection from endothelial dysfunction[67–71] and vascular inflammation[72] under conditions of metabolic and inflammatory stress.”
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 [57]
Nitrite metabolism can be activated by hypoxia, low pH and reactions with metalloproteins.
“Nitrite metabolism can be activated by hypoxia, low pH and reactions with metalloproteins[50–58].”
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 [57]
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Cites
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · see citing works
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074 · see citing works
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 4× · see citing works
“These limitations open the door to other molecules that can be a source of NO and nitrosative signaling, including the anion nitrite (NO2 - ) (55).”
BackgroundInfluentialNitrite 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 · see citing works
Self-citationMacrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite
Hibbs, J. B., Taintor, R. R., & Vavrin, Z. (1987) · Science · doi:10.1126/science.2432665 · Cited by 1,527 · see citing works
Papapetropoulos, A., García‐Cardeña, G., Madri, J. A., & Sessa, W. C. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119868 · Cited by 1,192 · see citing works
Stuehr, D. J., & Marletta, M. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.22.7738 · Cited by 1,126 · see citing works
Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension
PEPKEZABA, J. (1991) · The Lancet · doi:10.1016/0140-6736(91)92033-x · Cited by 1,055 · see citing works
Workgroup Report: Drinking-Water Nitrate and Health—Recent Findings and Research Needs
Ward, M. H., de Kok, T. M. C. M., Levallois, P., Brender, J. D., Guliš, G., Nolan, B. T., & VanDerslice, J. A. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.8043 · Cited by 892 · see citing works
Enzyme-independent formation of nitric oxide in biological tissues
Zweier, J. L., Wang, P., Samouilov, A., & Kuppusamy, P. (1995) · Nature Medicine · doi:10.1038/nm0895-804 · Cited by 788 · see citing works
Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn
Clark, R. H., Kueser, T. J., Walker, M. W., Southgate, W. M., Huckaby, J., Perez, J. A. R., Roy, B. J., Keszler, M., & Kinsella, J. P. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002173420704 · Cited by 726 · see citing works
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
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., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674 · cited 1× · see citing works
“showed a large effect in decrease of the infarct size when nitrite was applied during ischemia (23).”
MethodBenjamin, N., O'Driscoll, F., Dougall, H., Duncan, C., Smith, L., Golden, M., & McKenzie, H. (1994) · Nature · doi:10.1038/368502a0 · Cited by 665 · see citing works
Iyengar, R., Stuehr, D. J., & Marletta, M. A. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.18.6369 · Cited by 664 · see citing works
Intragastric nitric oxide production in humans: measurements in expelled air.
Lundberg, J. O., Weitzberg, E., Lundberg, J. M., & Alving, K. (1994) · Gut · doi:10.1136/gut.35.11.1543 · Cited by 661 · see citing works
Inorganic 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 · see citing works
The 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 · see citing works
Liu, X., Miller, M. J. S., Joshi, M. S., Thomas, D. D., & Lancaster, J. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2175 · Cited by 602 · see citing works
Shiva, S., Huang, Z., Grubina, R., Sun, J., Ringwood, L. A., MacArthur, P. H., Xu, X., Murphy, E., Darley-Usmar, V. M., & Gladwin, M. T. (2007) · Circulation Research · doi:10.1161/01.res.0000260171.52224.6b · Cited by 599 · see citing works
Effects 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 · see citing works
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 · see citing works
Ichinose, F., Roberts, J. D., & Zapol, W. M. (2004) · Circulation · doi:10.1161/01.cir.0000134595.80170.62 · Cited by 540 · see citing works
Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control
Huang, Z. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24650 · Cited by 520 · see citing works
Castello, P. R., David, P. S., McClure, T., Crook, Z., & Poyton, R. O. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.011 · Cited by 495 · see citing works
Hendgen-Cotta, U. B., Merx, M. W., Shiva, S., Schmitz, J., Becher, S., Klare, J. P., Steinhoff, H.-J., Goedecke, A., Schrader, J., Gladwin, M. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801336105 · Cited by 418 · see citing works
Self-citationBelikova, N. A., Vladimirov, Y. A., Osipov, A. N., Kapralov, A. A., Tyurin, V. A., Potapovich, M. V., Basova, L. V., Peterson, J., Kurnikov, I. V., & Kagan, V. E. (2006) · Biochemistry · doi:10.1021/bi0525573 · Cited by 398 · see citing works
Inhaled Nitric Oxide Therapy in Adults
Griffiths, M., & Evans, T. W. (2005) · New England Journal of Medicine · doi:10.1056/nejmra051884 · Cited by 392 · see citing works
Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis
Shiva, S., Wang, X., Ringwood, L. A., Xu, X., Yuditskaya, S., Annavajjhala, V., Miyajima, H., Hogg, N., Harris, Z. L., & Gladwin, M. T. (2006) · Nature Chemical Biology · doi:10.1038/nchembio813 · Cited by 359 · see citing works
Self-citationKinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites.
Doyle, M. P., Pickering, R. A., DeWeert, T. M., Hoekstra, J. W., & Pater, D. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43285-1 · Cited by 334 · see citing works
Dejam, A., Hunter, C. J., Tremonti, C., Pluta, R. M., Hon, Y. Y., Grimes, G., Partovi, K., Pelletier, M. M., Oldfield, E. H., Cannon, R. O., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.712133 · Cited by 334 · see citing works
Self-citationNitrates, nitrites and gastric cancer in Great Britain
Forman, D., Al-Dabbagh, S. A., & Doll, R. (1985) · Nature · doi:10.1038/313620a0 · Cited by 310 · see citing works
Nonenzymatic Nitric Oxide Production in Humans
Weitzberg, E., & Lundberg, J. O. N. (1998) · Nitric Oxide · doi:10.1006/niox.1997.0162 · Cited by 296 · see citing works
The functional nitrite reductase activity of the heme-globins
Gladwin, M. T., & Kim-Shapiro, D. B. (2008) · Blood · doi:10.1182/blood-2008-01-115261 · Cited by 293 · see citing works
Human neuroglobin functions as a redox-regulated nitrite reductase
Tiso, M., Tejero, J., Basu, S., Azarov, I., Wang, X., Simplaceanu, V., Frizzell, S., Jayaraman, T., Geary, L., Shapiro, C., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159541 · Cited by 287 · see citing works
Self-citationNitrite and nitrate are formed by endogenous synthesis in the human intestine
Tannenbaum, S. R., Fett, D., Young, V. R., Land, P. D., & Bruce, W. R. (1978) · Science · doi:10.1126/science.663630 · Cited by 284 · see citing works
Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator
Hunter, C. J., Dejam, A., Blood, A. B., Shields, H., Kim-Shapiro, D. B., Machado, R. F., Tarekegn, S., Mulla, N., Hopper, A. O., Schechter, A. N., et al. (2004) · Nature Medicine · doi:10.1038/nm1109 · Cited by 281 · see citing works
Self-citationCharacterization of the Magnitude and Kinetics of Xanthine Oxidase-catalyzed Nitrite Reduction
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011648200 · Cited by 280 · see citing works
Pluta, R. M. (2005) · JAMA · doi:10.1001/jama.293.12.1477 · Cited by 261 · see citing works
Reddy, D. S. A., Lancaster, J. R., & Cornforth, D. P. (1983) · Science · doi:10.1126/science.6308761 · Cited by 258 · see citing works
Jung, K.-H., Chu, K., Ko, S.-Y., Lee, S.-T., Sinn, D.-I., Park, D.-K., Kim, J.-M., Song, E.-C., Kim, M., & Roh, J.-K. (2006) · Stroke · doi:10.1161/01.str.0000245116.40163.1c · Cited by 253 · see citing works
Sickle cell disease vasculopathy: A state of nitric oxide resistance
Wood, K. C., Hsu, L. L.-Y., & Gladwin, M. T. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.01.008 · Cited by 246 · see citing works
Verrax, J., & Calderón, P. B. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.016 · Cited by 232 · see citing works
Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin
Basu, S., Grubina, R., Huang, J., Conradie, J., Huang, Z., Jeffers, A., Jiang, A., He, X., Azarov, I., Seibert, R., et al. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.46 · Cited by 224 · see citing works
Self-citationEvidence for in vivo transport of bioactive nitric oxide in human plasma
Rassaf, T., Preik, M., Kleinbongard, P., Lauer, T., Heiß, C., Strauer, B. E., Feelisch, M., & Kelm, M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14995 · Cited by 224 · see citing works
Waud, W. R., & Rajagopalan, K. V. (1976) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(76)90088-6 · Cited by 216 · see citing works
Nitrite reductase activity of cytochrome c
Basu, S., Azarova, N. A., Font, M. D., King, S. B., Hogg, N., Gladwin, M. T., Shiva, S., & Kim-Shapiro, D. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806934200 · Cited by 214 · see citing works
Self-citationAamand, R., Dalsgaard, T., Jensen, F. B., Simonsen, U., Roepstorff, A., & Fago, A. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00525.2009 · Cited by 213 · see citing works
Webb, A. J., Milsom, A. B., Rathod, K. S., Chu, W. L., Qureshi, S., Lovell, M. J., Lecomte, F. M. J., Perrett, D., Raimondo, C., Khoshbin, E., et al. (2008) · Circulation Research · doi:10.1161/circresaha.108.175810 · Cited by 203 · see citing works
Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics
DEZFULIAN, C., RAAT, N., SHIVA, S., & GLADWIN, M. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.05.001 · Cited by 198 · cited 1× · see citing works
“Nitrite has protective effects in different ischemia reperfusion injury models (19).”
BackgroundGladwin, M. T., Grubina, R., & Doyle, M. P. (2009) · Accounts of Chemical Research · doi:10.1021/ar800089j · Cited by 194 · see citing works
Zuckerbraun, B. S., Shiva, S., Ifedigbo, E., Mathier, M. A., Mollen, K. P., Rao, J., Bauer, P. M., Choi, J. J. W., Curtis, E., Choi, A. M. K., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.891077 · Cited by 192 · see citing works
Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis
Kumar, D., Branch, B. G., Pattillo, C. B., Hood, J., Thoma, S., Simpson, S., Illum, S., Arora, N., Chidlow, J. H., Langston, W., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711480105 · Cited by 187 · see citing works
Reactive oxygen and nitrogen species in pulmonary hypertension
Tabima, D. M., Frizzell, S. A., & Gladwin, M. T. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.041 · Cited by 186 · see citing works
Gonzalez, F. M., Shiva, S., Vincent, P. S., Ringwood, L. A., Hsu, L.-Y., Hon, Y. Y., Aletras, A. H., Cannon, R. O., Gladwin, M. T., & Arai, A. E. (2008) · Circulation · doi:10.1161/circulationaha.107.748814 · Cited by 175 · see citing works
Dezfulian, C., Shiva, S., Alekseyenko, A., Pendyal, A., Beiser, D. G., Munasinghe, J. P., Anderson, S. A., Chesley, C. F., Vanden Hoek, T. L., & Gladwin, M. T. (2009) · Circulation · doi:10.1161/circulationaha.109.853267 · Cited by 174 · see citing works
Nitric oxide synthase reduces nitrite to NO under anoxia
Vanin, A. F., Bevers, L. M., Slama-Schwok, A., & van Faassen, E. E. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6374-2 · Cited by 151 · see citing works
Characterization of the effects of oxygen on xanthine oxidase-mediated nitric oxide formation
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314336200 · Cited by 146 · see citing works
INHALED NITRIC OXIDE FOR PULMONARY HYPERTENSION AFTER HEART TRANSPLANTATION
Ardehali, A. A., Hughes, K., Sadeghi, A., Esmailian, F., Marelli, D., Moriguchi, J., Hamilton, M. A., KOBASHIGAWA, J. A., & Laks, H. (2001) · Transplantation · doi:10.1097/00007890-200108270-00013 · Cited by 140 · see citing works
Nitrite–nitric oxide control of mitochondrial respiration at the frontier of anoxia
Benamar, A., Rolletschek, H., Borisjuk, L., Avelange‐Macherel, M., Curien, G., Mostefai, H. A., Andriantsitohaina, R., & Macherel, D. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.06.002 · Cited by 140 · see citing works
Li, H., Kundu, T. K., & Zweier, J. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.019125 · Cited by 126 · see citing works
Inhaled Nitric Oxide in Preterm Infants: A Systematic Review
Donohue, P., Gilmore, M. M., Cristofalo, E. A., Wilson, R. F., Weiner, J. Z., Lau, B. D., Robinson, K. A., & Allen, M. C. (2011) · PEDIATRICS · doi:10.1542/peds.2010-3428 · Cited by 123 · see citing works
Safety and Feasibility of Long-term Intravenous Sodium Nitrite Infusion in Healthy Volunteers
Pluta, R. M., Oldfield, E. H., Bakhtian, K. D., Fathi, A. R., Smith, R. K., DeVroom, H. L., Nahavandi, M., Woo, S., Figg, W. D., & Lonser, R. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014504 · Cited by 112 · see citing works
Inorganic nitrate and nitrite and control of blood pressure
Gilchrist, M., Shore, A. C., & Benjamin, N. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq309 · Cited by 110 · see citing works
Alef, M. J., Vallabhaneni, R., Carchman, E., Morris, S. M., Shiva, S., Wang, Y., Kelley, E. E., Tarpey, M. M., Gladwin, M. T., Tzeng, E., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44079 · Cited by 101 · see citing works
Self-citationZuckerbraun, B. S., George, M. P., & Gladwin, M. T. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq370 · Cited by 97 · see citing works
Champion, H. C., Bivalacqua, T. J., Greenberg, S. S., Giles, T. D., Hyman, A. L., & Kadowitz, P. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182225899 · Cited by 95 · see citing works
Moore, L. L., Bradlee, M. L., Singer, M. R., Qureshi, M. M., Buendia, J. R., & Daniels, S. R. (2012) · British Journal Of Nutrition · doi:10.1017/s000711451100715x · Cited by 94 · see citing works
Human xanthine oxidase converts nitrite ions into nitric oxide (NO)
Zhang, Z., Naughton, D. P., Blake, D. R., Benjamin, N., Stevens, C. R., Winyard, P. G., Symons, M. C. R., & Harrison, R. (1997) · Biochemical Society Transactions · doi:10.1042/bst025524s · Cited by 85 · see citing works
Inhaled Nitric Oxide for Modulation of Ischemia–Reperfusion Injury in Lung Transplantation
Botha, P., Jeyakanthan, M., Rao, J. N., Fisher, A. J., Prabhu, M., Dark, J. H., & Clark, S. C. (2007) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2007.08.008 · Cited by 80 · see citing works
Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study
Mack, A. K., McGowan II, V. R., Tremonti, C. K., Ackah, D., Barnett, C., Machado, R. F., Gladwin, M. T., & Kato, G. J. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07259.x · Cited by 64 · see citing works
Harris, C. M., & Massey, V. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28335 · Cited by 61 · see citing works
Casey, D. B., Badejo, A. M., Dhaliwal, J. S., Murthy, S. N., Hyman, A. L., Nossaman, B. D., & Kadowitz, P. J. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00543.2008 · Cited by 61 · see citing works
Intravesical Nitric Oxide Delivery for Prevention of Catheter-Associated Urinary Tract Infections
Carlsson, S., Weitzberg, E., Wiklund, P., & Lundberg, J. O. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.6.2352-2355.2005 · Cited by 59 · see citing works
Nitrite as a mediator of ischemic preconditioning and cytoprotection
Murillo, D., Kamga, C., Mo, L., & Shiva, S. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.01.003 · Cited by 57 · see citing works
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 · see citing works
Addition of Nitric Oxide to Oxygen Improves Cardiopulmonary Function in Patients With Severe COPD
Germann, P., Ziesche, R., Leitner, C., Röder, G., Urak, G., ZIMPFER, M., & Sladen, R. N. (1998) · CHEST Journal · doi:10.1378/chest.114.1.29 · Cited by 47 · see citing works
Shiva, S., Rassaf, T., Patel, R. P., & Gladwin, M. T. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq327 · Cited by 46 · see citing works
Pattillo, C. B., Bir, S. C., Rajaram, V., & Kevil, C. G. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq297 · Cited by 43 · see citing works
Ormerod, A., Shah, A., Li, H., Benjamin, N., Ferguson, G. P., & Leifert, C. (2011) · BMC Research Notes · doi:10.1186/1756-0500-4-458 · Cited by 36 · see citing works
Dellinger, R. P., Trzeciak, S. W., Criner, G. J., Zimmerman, J. L., Taylor, R. W., Usansky, H. H., Young, J. N., & Goldstein, B. (2012) · Critical Care · doi:10.1186/cc11215 · Cited by 35 · see citing works
Medieval Chinese Medicine: The Dunhuang Medical Manuscripts
Cullen, C., & Lo, V. (2004) · Medical Entomology and Zoology · Cited by 31 · see citing works
Evidence for in vivo transport of bioactive nitric oxide in human plasma
Rassaf, T., Preik, M., Kleinbongard, P., Lauer, T., Heiß, C., Strauer, B. E., Feelisch, M., & Kelm, M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200214995 · Cited by 30 · see citing works
Goret, L., Tanguy, S., Guiraud, I., Dauzat, M., & Obert, P. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.11.037 · Cited by 24 · see citing works
Effects of long term nitrite therapy on functional recovery in experimental ischemia model
Jung, K.-H., Chu, K., Lee, S.-T., Sunwoo, J.-S., Park, D.-K., Kim, J.-H., Kim, S., Lee, S. K., Kim, M., & Roh, J.-K. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.10.116 · Cited by 23 · see citing works
McCarty, M. F. (2010) · Medical Hypotheses · doi:10.1016/j.mehy.2009.12.020 · Cited by 19 · see citing works
Allylic Nitro Compounds as Nitrite Donors
Chakrapani, H., Gorczynski, M. J., & King, S. B. (2006) · Journal of the American Chemical Society · doi:10.1021/ja066011v · Cited by 17 · see citing works
Egemnazarov, B., SCHERMULY, R. T., Dahal, B. K., Elliott, G. T., Hoglen, N. C., Surber, M. W., Weißmann, N., Grimminger, F., Seeger, W., & Ghofrani, H. A. (2010) · Respiratory Research · doi:10.1186/1465-9921-11-81 · Cited by 16 · see citing works
Jung, K., Chu, K., Lee, S., Kim, J., Park, D.-K., Kim, M., Lee, S. K., & Roh, J. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.05.018 · Cited by 4 · see citing works
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The mononuclear molybdenum enzymes
Hille, R., Hall, J., & Basu, P. (2014) · Chemical Reviews · doi:10.1021/cr400443z · Cited by 1,738 · see citing works
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Daiber, A., Steven, S., Weber, A., Shuvaev, V. V., Muzykantov, V. R., Laher, I., Li, H., Lamas, S., & Münzel, T. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13517 · Cited by 501 · see citing works
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Baffi, C. W., Wood, L. G., Winnica, D., Strollo, P. J., Gladwin, M. T., Que, L. G., & Holguín, F. (2016) · CHEST Journal · doi:10.1016/j.chest.2015.12.034 · Cited by 236 · see citing works
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Klinger, J. R., Abman, S. H., & Gladwin, M. T. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201304-0686pp · Cited by 225 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
Self-citationSparacino-Watkins, C. E., Tejero, J., Sun, B., Gauthier, M. C., Thomas, J., Ragireddy, V., Merchant, B. A., Wang, J., Azarov, I., Basu, P., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.555177 · Cited by 169 · see citing works
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Miljkovic, J. L., Kenkel, I., Ivanović‐Burmazović, I., & Filipovic, M. R. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201305669 · Cited by 148 · see citing works
Cantú‐Medellín, N., & Kelley, E. E. (2013) · Nitric Oxide · doi:10.1016/j.niox.2013.02.081 · Cited by 148 · see citing works
Oleskin, A. V., & Shenderov, B. A. (2016) · Microbial Ecology in Health & Disease · doi:10.3402/mehd.v27.30971 · Cited by 145 · see citing works
The Nitric Oxide Pathway in Pulmonary Vascular Disease
Klinger, J. R., & Kadowitz, P. J. (2017) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2017.06.012 · Cited by 117 · see citing works
Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall
Billaud, M., Lohman, A. W., Johnstone, S. R., Biwer, L. A., Mutchler, S. M., & Isakson, B. E. (2014) · Pharmacological Reviews · doi:10.1124/pr.112.007351 · Cited by 110 · see citing works
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Münzel, T. F., Daiber, A., & Gori, T. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht249 · Cited by 99 · see citing works
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Maia, L. B., & Moura, J. J. G. (2015) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-014-1234-2 · Cited by 86 · see citing works
Münzel, T. F., & Daiber, A. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.11.003 · Cited by 86 · see citing works
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Kelley, E. E. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.05.004 · Cited by 78 · see citing works
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Park, M. S., Sandner, P., & Krieg, T. (2018) · Basic Research in Cardiology · doi:10.1007/s00395-018-0679-9 · Cited by 75 · see citing works
Inorganic nitrite supplementation for healthy arterial aging
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Zemke, A. C., Shiva, S., Burns, J. L., Moskowitz, S. M., Pilewski, J. M., Gladwin, M. T., & Bomberger, J. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.08.011 · Cited by 61 · see citing works
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Maia, L. B., & Moura, J. J. G. (2018) · Redox Biology · doi:10.1016/j.redox.2018.08.020 · Cited by 56 · see citing works
Tsikas, D. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2291336 · Cited by 54 · see citing works
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Bohlen, H. G. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140052 · Cited by 54 · see citing works
Rix, P. J., Vick, A., Attkins, N., Barker, G. E., Bott, A. W., Alcorn, H. W., Gladwin, M. T., Shiva, S., Bradley, S. P., Hussaini, A., et al. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-014-0201-y · Cited by 48 · see citing works
Hansen, T., Galougahi, K. K., Celermajer, D. S., Rasko, N. B., Tang, O., Bubb, K. J., & Figtree, G. A. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.05.005 · Cited by 48 · see citing works
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Profiling nitric oxide metabolites in patients with idiopathic pulmonary arterial hypertension
Zhang, R., Wang, X., Zhang, H., Sun, X., Zhao, Q., Wang, L., He, J., Jiang, X., Liu, J., & Jing, Z. (2016) · European Respiratory Journal · doi:10.1183/13993003.00245-2016 · Cited by 30 · see citing works
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Mizuno, S., Ishizaki, T., Toga, H., Sakai, A., Isakova, J. T., Talaibekova, E., Zamirbek, B., Kojonazarov, B. K., & Aldashev, A. A. (2015) · BioMed Research International · doi:10.1155/2015/196904 · Cited by 27 · see citing works
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Cronican, A. A., Frawley, K. L., Ahmed, H., Pearce, L. L., & Peterson, J. (2015) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.5b00015 · Cited by 26 · see citing works
Gorman, S., & Weller, R. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.616527 · Cited by 23 · see citing works
Guo, K., & Gao, H. (2021) · Advanced Biology · doi:10.1002/adbi.202100773 · Cited by 22 · see citing works
Nydegger, C., Martinelli, C., Marco, F. D., Bulfamante, G., von Segesser, L., Tozzi, P., Samaja, M., & Milano, G. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00289 · Cited by 21 · see citing works
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Lim, Y. J., Foo, T. C., Yeung, A. W. S., Tu, X., Ma, Y., Hawkins, C. L., Witting, P. K., Jameson, G. N. L., Terentis, A. C., & Thomas, S. R. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b01231 · Cited by 21 · see citing works
Antioxidant Therapy for the Treatment of Pulmonary Hypertension
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Li, B., Huang, Y., Luo, C., Peng, X., Jiao, Y., Zhou, L., Yin, J., & Liu, L. (2021) · Nutrients · doi:10.3390/nu13124544 · Cited by 20 · see citing works
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Feng, D., Christensen, J. T., Yetman, A. T., Lindsey, M. L., Singh, A. B., & Salomon, J. (2021) · Journal of Congenital Cardiology · doi:10.1186/s40949-021-00060-4 · Cited by 19 · see citing works
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Lewis, S. E., Rosencrance, C. B., DeVallance, E., Giromini, A. P., Williams, X. M., Oh, J., Schmidt, H. M., Straub, A. C., Chantler, P. D., Patel, R. P., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.07.012 · Cited by 17 · see citing works
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Hubbard, C. D., Chatterjee, D., Oszajca, M., Polaczek, J., Impert, O., Chrzanowska, M., Katafias, A., Puchta, R., & van Eldik, R. (2020) · Dalton Transactions · doi:10.1039/c9dt04620h · Cited by 14 · see citing works
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Chen, J., Xie, P., Huang, Y., & Gao, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020979 · Cited by 13 · see citing works
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Bohlen, H. G. (2015) · Comprehensive physiology · doi:10.1002/j.2040-4603.2015.tb00628.x · Cited by 12 · see citing works
Trabelsi, T., Yaghlane, S. B., Mogren, M. M. A., Francisco, J. S., & Hochlaf, M. (2016) · The Journal of Chemical Physics · doi:10.1063/1.4961313 · Cited by 13 · see citing works
On the role of HNS and HSN as light-sensitive NO-donors for delivery in biological media
Trabelsi, T., Linguerri, R., Yaghlane, S. B., Jaidane, N.-E., Al‐Mogren, M. M., Francisco, J. S., & Hochlaf, M. (2015) · The Journal of Chemical Physics · doi:10.1063/1.4932084 · Cited by 9 · see citing works
Bogue, A. L., Panmanee, W., McDaniel, C. T., Mortensen, J. E., Kamau, E. T., Actis, L. A., Johannigman, J. A., Schurr, M. J., Satish, L., Kotagiri, N., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0247513 · Cited by 8 · see citing works
Plasma nitrite/nitrate levels: a new biomarker for pulmonary arterial hypertension?
Klinger, J. R. (2016) · European Respiratory Journal · doi:10.1183/13993003.01542-2016 · Cited by 8 · see citing works
Bringing Nitric Oxide to the Molybdenum World—A Personal Perspective
Maia, L. B. (2023) · Molecules · doi:10.3390/molecules28155819 · Cited by 7 · see citing works
Molecular Basis of Nitrative Stress in the Pathogenesis of Pulmonary Hypertension
Evans, C. E., & Zhao, Y. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-63245-2_3 · Cited by 7 · see citing works
A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension
Walker, M., Moore, H., Ataya, A., Pham, A. T., Corris, P. A., Laubenbacher, R., & Bryant, A. J. (2024) · Pulmonary Circulation · doi:10.1002/pul2.12392 · Cited by 6 · see citing works
Nitrite Reduction with H2S/Thiol Mediated by Cobalt and Manganese Porphyrins in the Solid State
Martirosyan, G. G., Hovhannisyan, A. A., Harutyunyan, L. S., Aleksanyan, A. G., Iretskii, A. V., & Ford, P. C. (2025) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.4c02733 · Cited by 5 · see citing works
Cortés‐Puch, I., Sun, J., Schechter, A. N., Solomon, S. B., Park, J. W., Feng, J., Gilliard, C. N., Natanson, C., & Piknova, B. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.07.001 · Cited by 5 · see citing works
Garofalo, F., Amelio, D., Gattuso, A., Cerra, M. C., & Pellegrino, D. (2015) · Nitric Oxide · doi:10.1016/j.niox.2015.05.002 · Cited by 5 · see citing works
Allergic activation of mast cells.
Parker, C. W. (1986) · PubMed · Cited by 5 · see citing works
Pathogenic Mechanisms of Pulmonary Hypertension
Fraidenburg, D. R., & Yuan, J. X. ‐. (2014) · Springer eBooks · doi:10.1007/978-3-642-37078-6_203 · Cited by 4 · see citing works
Chronic Neonatal Lung Injury and Care Strategies to Decrease Injury
Jankov, R. P., & Tanswell, A. K. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781139680349.012 · Cited by 2 · see citing works
Plasma nitric oxide in dogs with pulmonary hypertension secondary or not to left-sided heart disease
Braz, J. B., Beluque, T., Ampuero, R. A. N., Canola, R. A. M., Batalhão, M. E., Cárnio, E. C., & Camacho, A. A. (2023) · Arquivo Brasileiro de Medicina Veterinária e Zootecnia · doi:10.1590/1678-4162-12528 · Cited by 1 · see citing works
Endothelial dysfunction: basis for many local and systemic conditions
Münzel, T. F., Hahad, O., & Daiber, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822546-2.00011-3 · Cited by 1 · see citing works
Kayser, B. (2013) · High Altitude Medicine & Biology · doi:10.1089/ham.2013.1057 · Cited by 1 · see citing works
A protective role of the nitrite/nitrate reductase system in ischemic stroke
Кузенков, В. С., & Krushynsky, A. L. (2015) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro201511512258-66
Tavasoli, F. (2014) · TSpace (University of Toronto)
Pulmonary Hypertension in Chronic Neonatal Lung Disease: Mechanisms and Targets
Jankov, R. P., & Tanswell, A. K. (2017) · Springer eBooks · doi:10.1007/978-3-319-67096-6_11
Gow, A. J., & Forman, H. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-404577-4.00018-7
Dezfulian, C. (2020) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000002216
HAMAMCIOĞLU, A. C., Öz, Z. S., & Bayraktaroğlu, T. (2022) · Turkish Journal of Diabetes and Obesity · doi:10.25048/tudod.1143765
- Authors
- Bueno, M., Wang, J., Mora, A. L., & Gladwin, M. T.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Gladwin, Mark T.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2013-05
- Volume
- 18
- Issue
- 14
- Pages
- 1797-1809
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC3619206
- OpenAlex
- W2030797425
- Cited by
- 68
- References
- 88
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 10 · 2015: 11 · 2014: 10 · 2013: 7
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- Hemophilia Center of Western Pennsylvania
- National Institutes of Health (PO1-HL-103455)
- National Heart, Lung, and Blood Institute (R01HL096973, P01HL103455, R01HL098032)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- pulmonary arterial hypertension, nitric oxide bioavailability, nitrite reductase, xanthine oxidase, hemoglobin, nitrate, L-arginine-NO pathway, nitrite therapy, hypoxia, pulmonary vascular resistance
- MeSH terms
- Animals, Humans, Hypertension, Pulmonary, Nitrates, Nitric Oxide, Nitrites, Vascular Diseases, Signal Transduction
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