NO generation from nitrite and its role in vascular control.

NO generated from L-arginine by NO synthases (NOSs) in the endothelium and in other cells plays a central role in several aspects of vascular biology. The biological activity of NO is acutely terminated by oxidation to nitrite and nitrate, and these compounds have long been considered only as inert end-products of NO. However, this dogma is now being challenged because recent research convincingly has shown that the nitrite ion can be recycled back to bioactive NO again in blood and tissues. Nitrite reduction to NO can occur via several routes involving enzymes, proteins, vitamins, or even simple protons. This pathway may serve as a backup system for NO generation in conditions such as hypoxia, in which the NOS/L-arginine system is compromised, but detrimental effects can also be foreseen. With this new knowledge, nitrate and nitrite should probably be viewed as storage pools for NO rather than inert waste products. Here we discuss novel aspects of nitrite-dependent NO generation in vivo and its role in vascular control.

[1]  Michiyo Shikishima,et al.  Nitrite is an alternative source of NO in vivo. , 2005, American journal of physiology. Heart and circulatory physiology.

[2]  David J Singel,et al.  Chemical physiology of blood flow regulation by red blood cells: the role of nitric oxide and S-nitrosohemoglobin. , 2005, Annual review of physiology.

[3]  E. Clementi,et al.  Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  T. Sobko,et al.  Gastrointestinal nitric oxide generation in germ-free and conventional rats. , 2004, American journal of physiology. Gastrointestinal and liver physiology.

[5]  W. Kaiser,et al.  Mitochondrial electron transport as a source for nitric oxide in the unicellular green alga Chlorella sorokiniana , 2004, FEBS letters.

[6]  A. Ahluwalia,et al.  Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Lundberg,et al.  Inorganic nitrate is a possible source for systemic generation of nitric oxide. , 2004, Free radical biology & medicine.

[8]  Jeff A. Cole,et al.  Nitrate, bacteria and human health , 2004, Nature Reviews Microbiology.

[9]  C. Piantadosi,et al.  How do red blood cells dilate blood vessels? , 2004, Circulation Research.

[10]  N. Bryan,et al.  Bound NO in human red blood cells: fact or artifact? , 2004, Nitric oxide : biology and chemistry.

[11]  M. Gladwin,et al.  NO contest: nitrite versus S-nitroso-hemoglobin. , 2004, Circulation research.

[12]  J. Hare,et al.  Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications , 2004, The Journal of physiology.

[13]  T. Rassaf,et al.  Circulating NO pool: assessment of nitrite and nitroso species in blood and tissues. , 2004, Free radical biology & medicine.

[14]  D. Giustarini,et al.  Adaptation of the Griess Reaction for Detection of Nitrite in Human Plasma , 2004, Free radical research.

[15]  M. Yoshizumi,et al.  Malfunction of vascular control in lifestyle-related diseases: formation of systemic hemoglobin-nitric oxide complex (HbNO) from dietary nitrite. , 2004, Journal of pharmacological sciences.

[16]  M. Phillipson,et al.  Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. , 2004, The Journal of clinical investigation.

[17]  M. Gladwin,et al.  Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation , 2003, Nature Medicine.

[18]  D. Abernethy,et al.  Active Nitric Oxide Produced in the Red Cell under Hypoxic Conditions by Deoxyhemoglobin-mediated Nitrite Reduction* , 2003, Journal of Biological Chemistry.

[19]  N. Bryan,et al.  Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. , 2003, Free radical biology & medicine.

[20]  A. Kozlov,et al.  Various intracellular compartments cooperate in the release of nitric oxide from glycerol trinitrate in liver , 2003, British journal of pharmacology.

[21]  J. Stamler,et al.  Reply to "NO adducts in mammalian red blood cells: too much or too little?" , 2003, Nature Medicine.

[22]  N. Bryan,et al.  NO adducts in mammalian red blood cells: too much or too little? , 2003, Nature Medicine.

[23]  C. Rice-Evans,et al.  The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans. , 2003, Free radical biology & medicine.

[24]  Xiaoping Liu,et al.  Characterization of the magnitude and kinetics of xanthine oxidase-catalyzed nitrate reduction: evaluation of its role in nitrite and nitric oxide generation in anoxic tissues. , 2003, Biochemistry.

[25]  J. Stamler,et al.  Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the β subunits , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  N. Bryan,et al.  Chemical nature of nitric oxide storage forms in rat vascular tissue , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  G. Heusch,et al.  Plasma Nitrosothiols Contribute to the Systemic Vasodilator Effects of Intravenously Applied NO: Experimental and Clinical Study on the Fate of NO in Human Blood , 2002, Circulation research.

[28]  N. Benjamin,et al.  The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans. , 2002, Nitric oxide : biology and chemistry.

[29]  J. Stamler,et al.  Nitric oxide in the human respiratory cycle , 2002, Nature Medicine.

[30]  Xiaoping Liu,et al.  Nitric Oxide Uptake by Erythrocytes Is Primarily Limited by Extracellular Diffusion Not Membrane Resistance* , 2002, The Journal of Biological Chemistry.

[31]  J. Liao,et al.  Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Stamler,et al.  Identification of the enzymatic mechanism of nitroglycerin bioactivation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[33]  A. Meneshian,et al.  The Physiology of Endothelial Xanthine Oxidase: From Urate Catabolism to Reperfusion Injury to Inflammatory Signal Transduction , 2002, Microcirculation.

[34]  T. Rassaf,et al.  Evidence for in vivo transport of bioactive nitric oxide in human plasma. , 2002, The Journal of clinical investigation.

[35]  Jorge D. Erusalimsky,et al.  Does nitric oxide modulate mitochondrial energy generation and apoptosis? , 2002, Nature Reviews Molecular Cell Biology.

[36]  M. B. Davies,et al.  Circulating nitrite anions are a directly acting vasodilator and are donors for nitric oxide. , 2002, Clinical science.

[37]  T. Rassaf,et al.  Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[38]  J. Liao,et al.  Modulation of nitric oxide bioavailability by erythrocytes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  M. Gladwin,et al.  Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. , 2001, The Journal of clinical investigation.

[40]  Xiaoping Liu,et al.  Characterization of the Magnitude and Kinetics of Xanthine Oxidase-catalyzed Nitrite Reduction , 2001, The Journal of Biological Chemistry.

[41]  J. Stamler,et al.  Export by red blood cells of nitric oxide bioactivity , 2001, Nature.

[42]  E. Weitzberg,et al.  Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation. , 2001, Acta physiologica Scandinavica.

[43]  S Moncada,et al.  The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Gladwin,et al.  Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Gladwin,et al.  Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[46]  R. Eisenthal,et al.  Reduction of Nitrite to Nitric Oxide Catalyzed by Xanthine Oxidoreductase* , 2000, The Journal of Biological Chemistry.

[47]  E. Cadenas,et al.  Regulation of Mitochondrial Respiration by Oxygen and Nitric Oxide , 2000, Annals of the New York Academy of Sciences.

[48]  H. Redl,et al.  Mitochondria Recycle Nitrite Back to the Bioregulator Nitric Monoxide , 2022 .

[49]  M. Haas,et al.  Persistent Antihypertensive Effect of Oral Nitrite Supplied up to One Year via the Drinking Water in Spontaneously Hypertensive Rats , 1999, Arzneimittelforschung.

[50]  L. Ignarro,et al.  Different plasma levels of nitric oxide in arterial and venous blood. , 1999, Clinical physiology.

[51]  J. Liao,et al.  Intravascular flow decreases erythrocyte consumption of nitric oxide. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[52]  A. Kozlov,et al.  Nitrite reductase activity is a novel function of mammalian mitochondria , 1999, FEBS letters.

[53]  R. Heller,et al.  l-Ascorbic Acid Potentiates Nitric Oxide Synthesis in Endothelial Cells* , 1999, The Journal of Biological Chemistry.

[54]  J. Lundberg,et al.  Salivary contribution to exhaled nitric oxide. , 1999, The European respiratory journal.

[55]  J. Keaney,et al.  Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. , 1998, Circulation research.

[56]  D. Naughton,et al.  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. , 1998, Biochemical and biophysical research communications.

[57]  Xiaoping Liu,et al.  Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes* , 1998, The Journal of Biological Chemistry.

[58]  Reutov Vp,et al.  NO-SYNTHASE AND NITRITE-REDUCTASE COMPONENTS OF NITRIC OXIDE CYCLE , 1998 .

[59]  L. Ghiadoni,et al.  Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. , 1998, Circulation.

[60]  P. Kubes,et al.  Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds. , 1998, The Journal of clinical investigation.

[61]  R. Eisenthal,et al.  Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions , 1998, FEBS letters.

[62]  E. Weitzberg,et al.  Nonenzymatic nitric oxide production in humans. , 1998, Nitric oxide : biology and chemistry.

[63]  V. Reutov,et al.  NO-synthase and nitrite-reductase components of nitric oxide cycle. , 1998, Biochemistry. Biokhimiia.

[64]  N. Takizawa,et al.  Nitrosyl hemoglobin in blood of normoxic and hypoxic sheep during nitric oxide inhalation. , 1998, American journal of physiology. Heart and circulatory physiology.

[65]  L. Engstrand,et al.  Urinary nitrite: more than a marker of infection. , 1997, Urology.

[66]  D. Naughton,et al.  Human xanthine oxidase converts nitrite ions into nitric oxide (NO). , 1997, Biochemical Society transactions.

[67]  I. T. Demchenko,et al.  Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. , 1997, Science.

[68]  J. Zweier,et al.  Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Farris K. Timimi,et al.  Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. , 1997, Circulation.

[70]  A. Gow,et al.  A Novel Reaction Mechanism for the Formation of S-Nitrosothiol in Vivo* , 1997, The Journal of Biological Chemistry.

[71]  R. Weller,et al.  Nitric oxide is generated on the skin surface by reduction of sweat nitrate. , 1996, The Journal of investigative dermatology.

[72]  S. Snyder,et al.  Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[73]  C. C. Smith,et al.  Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense , 1996, Antimicrobial agents and chemotherapy.

[74]  J. Stamler,et al.  S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control , 1996, Nature.

[75]  J. Cole.  Nitrate reduction to ammonia by enteric bacteria: redundancy, or a strategy for survival during oxygen starvation? , 1996, FEMS microbiology letters.

[76]  C. C. Smith,et al.  Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense. , 1996, Antimicrobial agents and chemotherapy.

[77]  Farris K. Timimi,et al.  Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. , 1996, The Journal of clinical investigation.

[78]  J. Zweier,et al.  Enzyme-independent formation of nitric oxide in biological tissues , 1995, Nature Medicine.

[79]  C. Leifert,et al.  Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate , 1995, Nature Medicine.

[80]  S. Moncada,et al.  The L-arginine:nitric oxide pathway is the major source of plasma nitrite in fasted humans. , 1995, Biochemical and biophysical research communications.

[81]  H. Thöni,et al.  Antihypertensive effect of oral nitrite uptake in the spontaneously hypertensive rat. , 1995, Arzneimittel-Forschung.

[82]  E. Weitzberg,et al.  Intragastric nitric oxide production in humans: measurements in expelled air. , 1994, Gut.

[83]  N. Benjamin,et al.  Stomach NO synthesis , 1994, Nature.

[84]  Y. Moriwaki,et al.  Purification and immunohistochemical tissue localization of human xanthine oxidase. , 1993, Biochimica et biophysica acta.

[85]  J. Stamler,et al.  Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[86]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[87]  P. Kubes,et al.  Nitric oxide: an endogenous modulator of leukocyte adhesion. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[88]  H. Thöni,et al.  Hypothesis: the effect of oral nitrite on blood pressure in the spontaneously hypertensive rat. Does dietary nitrate mitigate hypertension after conversion to nitrite? , 1990, Journal of the American College of Nutrition.

[89]  B. Freeman,et al.  Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[90]  S. Moncada,et al.  ENDOGENOUS NITRIC OXIDE INHIBITS HUMAN PLATELET ADHESION TO VASCULAR ENDOTHELIUM , 1987, The Lancet.

[91]  U. Förstermann,et al.  Endothelium-derived relaxing factor from cultured human endothelial cells inhibits aggregation of human platelets. , 1987, Thrombosis research.

[92]  M. Doyle,et al.  Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. , 1981, The Journal of biological chemistry.

[93]  L. Ignarro,et al.  Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. , 1981, The Journal of pharmacology and experimental therapeutics.

[94]  M. Doyle,et al.  Oxidation of nitrogen oxides by bound dioxygen in hemoproteins. , 1981, Journal of inorganic biochemistry.

[95]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[96]  Z. Alikulov,et al.  [Nitrate and nitrite reductase activity of milk xanthine oxidase]. , 1980, Biokhimiia.

[97]  F. Murad,et al.  Effects of sodium nitroprusside, nitroglycerin, and sodium azide on levels of cyclic nucleotides and mechanical activity of various tissues. , 1977, Journal of cyclic nucleotide research.

[98]  F. Murad,et al.  Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. , 1977, Journal of cyclic nucleotide research.

[99]  G. Eisenbrand,et al.  Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. , 1976, Food and cosmetics toxicology.

[100]  R. Furchgott,et al.  Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. , 1953, The Journal of pharmacology and experimental therapeutics.