nitric oxide

An important messenger molecule in mammals and other animals. It can be toxic or beneficial, depending on the amount and where in the body it is released. Initial research into the chemistry of nitric oxide (NO) was motivated by its production in car engines, which results in photochemical smog and acid rain. In the late 1980s, researchers in immunology, cardiovascular pharmacology, neurobiology, and toxicology discovered that nitric oxide is a crucial physiological messenger molecule. Nitric oxide is now thought to play a role in blood pressure regulation, control of blood clotting, immune defense, digestion, the senses of sight and smell, and possibly learning and memory. Nitric oxide may also participate in disease processes such as diabetes, stroke, hypertension, impotence, septic shock, and long-term depression. See also Immunology.

Most cellular messengers are large, unreactive biomolecules that make specific contacts with their targets. In contrast, nitric oxide is a small molecule that contains a free radical—that is, an unpaired electron—making it very reactive. Nitric oxide can freely diffuse through aqueous solutions or membranes, reacting rapidly with metal centers in cellular proteins and with reactive groups in other cellular molecules.

Nitric oxide is produced in the body by an enzyme called nitric oxide synthase, which converts the amino acid L-arginine to nitric oxide and L-citrulline. There are three types of nitric oxide synthase: brain, endothelial, and inducible. Both brain and endothelial enzymes are constitutive, that is, they are always present in cells, while the production of inducible nitric oxide synthase can be turned on or off when a system needs nitric oxide. After nitric oxide is produced in specific areas of the body by nitric oxide synthase, it diffuses to nearby cells. Nitric oxide then reacts preferentially in the interior of these cells with the metal centers of proteins. Nitric oxide binds specifically to the iron (Fe) atom of the heme group in proteins; it can also interact with other metal sites in proteins as well as with the thiol group (SH) of the amino acid cysteine. The interaction of nitric oxide with these proteins causes a cascade of intracellular events that leads to specific physiological changes within cells. For example, nitric oxide causes the smooth muscle cells surrounding blood vessels to relax, decreasing blood pressure. Nitric oxide plays an important role in the central and peripheral nervous systems; the overproduction of nitric oxide in brain tissues has been implicated in stroke and other neurological problems.

Nitric oxide also functions as an important agent in the immune system by killing invading bacterial cells. Nitric oxide released by macrophages can inhibit important cellular processes in the bacteria, including deoxyribonucleic acid (DNA) synthesis and respiration, by binding to and destroying iron-sulfur centers in key enzymes in these pathways.

Although nitric oxide production in the immune system serves a crucial biological function, there can be adverse effects when too much nitric oxide is produced. During a massive bacterial infection, excess nitric oxide can go into the vascular system, causing a dramatic decrease in blood pressure, which may lead to possibly fatal septic shock. Thus, scientists are working on drugs that can selectively inhibit the inducible form of nitric oxide synthase in order to avoid the harmful effects produced by excess nitric oxide without interfering with useful nitric oxide pathways.

Two strands of research in the late 1970s led to a revolution in biology. Robert Furchgott was unravelling a paradox concerning the well-known neurotransmitter acetylcholine: when injected intravenously it lowers blood pressure, showing that the body's blood vessels are relaxing, but when applied directly to blood vessels in isolation, outside the body, acetylcholine normally makes them contract. Furchgott showed that the response of blood vessels depended critically on the innermost layer of cells lining the vessel — the endothelium. When the endothelium was present, acetylcholine relaxed blood vessels, but when it was removed they contracted. Acetylcholine was shown to cause the release of a diffusible factor from endothelium, and it was this endothelium-derived relaxing factor (EDRF) — its nature then unknown — which relaxed the blood vessels.

Meanwhile, Ferid Murad was investigating how blood vessels are relaxed by the nitrovasodilators (e.g. glyceryl trinitrate, amyl nitrite) used in the treatment of angina. He found that these compounds increase the levels of cyclic GMP (known to promote relaxation) inside the smooth muscle cells of the vessels, probably by generating the substance nitric oxide (more correctly called nitrogen monoxide; NO).

It was soon shown that EDRF also increases the levels of cyclic GMP in smooth muscle, and the two lines of research converged when it was found that various agents, including haemoglobin and the dye methylene blue, inhibit the action both of EDRF and of the nitrovasodilators. By 1987, Furchgott and Louis Ignarro were suggesting that EDRF and NO were one and the same. This was confirmed by Salvador Moncada, who showed that NO is synthesized from the dietary amino acid L-arginine.

It then became evident that the endothelium of blood vessels was not the only site where NO is made. The enzyme nitric oxide synthase (NOS), which uses L-arginine, oxygen, and cofactors to make NO, exists in three forms: neuronal NOS (nNOS), from nerve cells; inducible NOS (iNOS), in inflammatory and other cells when the body's defence mechanisms are activated; and endothelial NOS (eNOS). nNOS and eNOS are ‘constitutive’ enzymes — that is, they are always present in their cells — and they are activated by increases in the intracellular concentration of calcium ions. iNOS is produced in many cells in response to bacterial infection and other circumstances (such as rheumatoid arthritis) when the immune system is activated; it is not regulated by calcium.

Nitric oxide is a tiny molecule. It is a gas, but dissolves in the fluids in and around cells. It is a free radical (sometimes denoted •NO to show that it has an unpaired electron, which makes it react very readily with other molecules). In particular, NO reacts with the radical anion, superoxide (•O^2-), to form peroxynitrite (ONOO^-), which can damage cellular DNA and hence cause cell death. Thus, excess NO can cause damage to cells. In some situations this is valuable: for instance, cells of the immune system use NO to kill invading bacteria. However, it can also be dangerous. After a stroke, for example, the nerve cells that have been deprived of oxygen fail to control their intracellular calcium; this rises and triggers a massive synthesis of NO by nNOS activation, leading to peroxynitrite production and the death of surrounding neurons. Peroxynitrite also oxidizes low density lipoproteins (LDL), which carry cholesterol in the blood, and oxidized LDL promotes atherosclerosis of blood vessels.

In septicaemia (blood poisoning), bacteria circulate in large numbers in the blood, and, in response, much NO is produced by many types of cells, including the muscle cells of the blood vessels this causes the blood vessels to relax. This leads to a severe fall in blood pressure, septic shock, which is difficult to reverse with agents such as adrenaline and dopamine, which normally increase blood pressure by constricting blood vessels. Septicaemia causes many deaths each year, and inhibition of NO synthesis appeared to be a promising treatment. But early attempts using inhibitors of NOS were largely unsuccessful. However, these were not selective for the relevant type (iNOS) and simultaneous inhibition of eNOS was deleterious to organ function. The increase in iNOS activity in inflammation can be inhibited by glucocorticoids (e.g. prednisolone, corticosterone), which explains part of their anti-inflammatory action, but they have no effect on the level of enzyme once it has been made. Thus the search is on for selective iNOS inhibitors which will leave nNOS and eNOS uninhibited.

NO has a good side and a bad side. While excess NO in septicaemia, inflammation, and stroke causes severe damage, localized production of small quantities of NO is essential for normal body function. Endothelial NOS maintains blood vessel function, and inhibition of this enzyme increases blood pressure. Indeed, hypertension is associated with decreased effectiveness of endothelial NO mechanisms. In blood vessels NO also regulates multiplication of muscle cells. Coronary artery bypass surgery sometimes fails because of narrowing of the newly replaced vessels; this is caused by thickening of their walls through muscle cell proliferation — thought to be due to decreased local production of NO as a result of endothelial damage during the surgery.

NO acts as a neurotransmitter in nerves involved in controlling a number of ‘vegetative’ functions, including operation of the sphincters in the gut and erection of the penis. Viagra (Sildenafil) works by prolonging the actions of NO released from penile nerves. In the brain, NO could even be involved in the formation of memory. ‘Long-term potentiation’ — the increase in strength of synapses in the hippocampus, as a result of strong stimulation which is thought to underlie certain forms of memory — is blocked by drugs that inhibit NO synthesis.

This small inorganic molecule, which was probably best known to the general public as a pollutant in car exhausts, became the biological molecule of the 1990s. Its importance was recognized by the award of a Nobel Prize to Furchgott, Ignarro, and Murad in 1998 ‘for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system’.

— C. Robin Hiley

See also blood vessels.

Brand names: INOmax®

Chemical formula:

Español:
• Gas para inhalación de óxido nítrico

Nitric Oxide inhalation gas

What is nitric oxide inhalation gas?

NITRIC OXIDE (INOmax™) is a drug that relaxes blood vessels in the lungs. It decreases blood pressure in the lungs and helps them to work better. Generic nitric oxide inhalation gas is not available.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• bleeding problems
• heart defect
• heart failure
• low platelet counts
• lung infection or chronic lung disease
• methemoglobin reductase deficiency
• an unusual or allergic reaction to nitric oxide, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Nitric oxide is breathed in while you are on a breathing machine. It is given by a trained health care professional in a hospital setting.

What drug(s) may interact with nitric oxide?

• monoamine oxidase inhibitors (Azilect®, Eldepryl®, Emsam®, Marplan®, Nardil®, Parnate®, Zelapar™)
• nitroglycerin
• nitroprusside

Tell your prescriber or health care professional about all other medicines that you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking nitric oxide?

Your condition will be closely monitored while you receive nitric oxide.

What side effects may I notice from receiving nitric oxide?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• blood in the urine
• high blood sugar
• increased difficulty breathing
• infection
• low blood pressure
• skin infection

Where can I keep my medicine?

This does not apply. Inhaled nitric oxide is only given in a hospital setting.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

For more information on nitric oxide, visit Britannica.com.

A compound released during exercise by the action of an enzyme, nitric oxide synthase, in cells lining arteries. Nitric oxide causes the arteries to dilate and prolongs vasodilation, thereby facilitating blood flow to muscle cells. Nitric oxide is used to treat people with obstructive pulmonary disease. Purveyors of dietary supplements containing substances (e.g. L-arginine) that increase nitric oxide levels in the blood, claim that the supplements enhance athletic performance by enabling nutritionally rich blood to flow more easily to skeletal muscles. Sometimes these supplements are marketed as ‘haemodilators’. Scientific studies carried out in 2004 indicate that nitric oxide supplements have no significant ergogenic effect on healthy individuals, and taking large doses of supplements could be dangerous to health.

Not to be confused with nitrous oxide.

For other uses, see NO.

Nitric oxide
Identifiers
CAS number	10102-43-9 Y
PubChem	145068
UN number	1660
DrugBank	DB00435
KEGG	C00533
ChEBI	16480
RTECS number	QX0525000
ATC code	R07AX01
InChI	1/NO/c1-2
InChI key	MWUXSHHQAYIFBG-UHFFFAOYAI
Properties
Molecular formula	NO
Molar mass	30.006 g/mol
Appearance	colourless gas paramagnetic
Density	1.269 g/cm3 (liquid) 1.3402 g/l (gas)
Melting point	−163.6 °C, 110 K, -262 °F
Boiling point	−150.8 °C, 122 K, -239 °F
Solubility in water	7.4 ml/100 ml (STP)
Solubility	soluble in alcohol, CS2
Refractive index (nD)	1.0002697
Structure
Molecular shape	linear, C∞v
Thermochemistry
Std enthalpy of formation ΔfHo298	+90.29 kJ/mol
Standard molar entropy So298	210.76 J K−1 mol−1
Pharmacology
Bioavailability	good
Routes of administration	Inhalation
Metabolism	via pulmonary capillary bed
Elimination half-life	2–6 seconds
Hazards
MSDS	External MSDS
EU Index	Not listed
Main hazards	Toxic
NFPA 704	0 3 0 OX
Flash point	Non-flammable
Related compounds
Related nitrogen oxides	Nitrous oxide Dinitrogen trioxide Nitrogen dioxide Dinitrogen tetroxide Dinitrogen pentoxide
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Nitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry. It is also an air pollutant produced by cigarette smoke, automobile engines and power plants.

NO is an important messenger molecule involved in many physiological and pathological processes within the mammalian body both beneficial and detrimental.^[1] Appropriate levels of NO production are important in protecting an organ such as the liver from ischemic damage. However sustained levels of NO production result in direct tissue toxicity and contribute to the vascular collapse associated with septic shock, whereas chronic expression of NO is associated with various carcinomas and inflammatory conditions including juvenile diabetes, multiple sclerosis, arthritis and ulcerative colitis.^[2]

Nitric oxide should not be confused with nitrous oxide (N₂O), a general anaesthetic and greenhouse gas, or with nitrogen dioxide (NO₂), which is another air pollutant. The nitric oxide molecule is a free radical, which is relevant to understanding its high reactivity.

Despite being a simple molecule, NO is a fundamental player in the fields of neuroscience, physiology, and immunology, and was proclaimed “Molecule of the Year” in 1992.^[3]

Contents 1 Reactions 1.1 Preparation 1.2 Coordination chemistry 1.3 Measurement of nitric oxide concentration 2 Production environmental effects 3 Technical applications 3.1 Miscellaneous applications 4 Biological functions 4.1 Mechanism of action 4.2 Use in pediatric intensive care 4.3 Pharmacology 5 See also 6 References 7 Further reading 8 External links

Reactions

• When exposed to oxygen, NO is converted into nitrogen dioxide.

2 NO + O₂ → 2 NO₂

This conversion has been speculated as occurring via the ONOONO intermediate. In water, NO reacts with oxygen and water to form HNO₂ or nitrous acid. The reaction is thought to proceed via the following stoichiometry:

4 NO + O₂ + 2 H₂O → 4 HNO₂

• NO will react with fluorine, chlorine, and bromine to form the XNO species, known as the nitrosyl halides, such as nitrosyl chloride. Nitrosyl iodide can form but is an extremely short lived species and tends to reform I₂.

2 NO + Cl₂ → 2 NOCl

• Nitroxyl (HNO) is the reduced form of nitric oxide.

• Nitric oxide reacts with acetone and an alkoxide to a diazeniumdiolate or nitrosohydroxylamine and Methyl acetate:^[4]

This is a very old reaction (1898) but of interest today in NO prodrug research. Nitric oxide can also react directly with sodium methoxide, forming sodium formate and nitrous oxide.^[5]

Preparation

• Commercially, NO is produced by the oxidation of ammonia at 750°C to 900°C (normally at 850°C) in the presence of platinum as catalyst:

4 NH₃ + 5 O₂ → 4 NO + 6 H₂O

The uncatalyzed endothermic reaction of O₂ and N₂, which is performed at high temperature (>2000°C) with lightning has not been developed into a practical commercial synthesis (see Birkeland–Eyde process):

N₂ + O₂ → 2 NO

• In the laboratory, it is conveniently generated by reduction of nitric acid with copper:

8 HNO₃ + 3 Cu → 3 Cu(NO₃)₂ + 4 H₂O + 2 NO

• or by the reduction of nitrous acid in the form of sodium nitrite or potassium nitrite:

2 NaNO₂ + 2 NaI + 2 H₂SO₄ → I₂ + 4 NaHSO₄ + 2 NO

2 NaNO₂ + 2 FeSO₄ + 3 H₂SO₄ → Fe₂(SO₄)₃ + 2 NaHSO₄ + 2 H₂O + 2 NO

3 KNO₂ (l) + KNO₃ (l) + Cr₂O₃(s) → 2 K₂CrO₄(s) + 4 NO (g)

The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments.

• So-called NONOate compounds are also used for NO generation.

Coordination chemistry

Main article: metal nitrosyl

NO forms complexes with all transition metals to give complexes called metal nitrosyls. The most common bonding mode of NO is the terminal linear type (M-NO). The angle of the M-N-O group can vary from 160° to 180° but are still termed as "linear". In this case, the NO group is considered a 3-electron donor under the covalent (neutral) method of electron counting, or a 2-electron donor under the ionic method.^[6] In the case of a bent M-N-O conformation, the NO group can be considered a one-electron donor using neural counting, or a 2-electron donor using ionic counting.^[7]One can view such complexes as derived from NO⁺, which is isoelectronic with CO.

Nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M-N-O group is characterized by an angle between 120° and 140°.

The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries.

Measurement of nitric oxide concentration

Nitric oxide (white) in conifer cells, visualized using DAF-2 DA (diaminofluorescein diacetate)

The concentration of nitric oxide can be determined using a simple chemiluminescent reaction involving ozone:^[8] A sample containing nitric oxide is mixed with a large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide. This reaction also produces light (chemiluminescence), which can be measured with a photodetector. The amount of light produced is proportional to the amount of nitric oxide in the sample.

NO + O₃ → NO₂ + O₂ + light

Other methods of testing include electroanalysis(amperometric approach), where NO reacts with an electrode to induce a current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron-dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with Electron Paramagnetic Resonance (EPR).^[9][10]

A group of fluorescent dye indicators that are also available in acetylated form for intracellular measurements exist. The most common compound is 4,5-diaminofluorescein (DAF-2).^[3]

Production environmental effects

From a thermodynamic perspective, NO is unstable with respect to O₂ and N₂, although this conversion is very slow at ambient temperatures in the absence of a catalyst. Because the heat of formation of NO is endothermic, its synthesis from molecular nitrogen and oxygen requires elevated temperatures, >1000°C. A major natural source is lightning. The use of internal combustion engines has drastically increased the presence of nitric oxide in the environment. One purpose of catalytic converters in cars is to minimize NO emission by catalytic reversion to O₂ and N₂.

Nitric oxide in the air may convert to nitric acid, which has been implicated in acid rain. Furthermore, both NO and NO₂ participate in ozone layer depletion. Nitric oxide is a small highly diffusible gas and a ubiquitous bioactive molecule.

Technical applications

Although NO has relatively few direct uses, it is produced on a massive scale as an intermediate in the Ostwald process for the synthesis of nitric acid from ammonia. In 2005, the US alone produced 6M metric tons of nitric acid.^[11] It finds use in the semiconductor industry for various processes. In one of its applications it is used along with nitrous oxide to form oxynitride gates in CMOS devices.

Miscellaneous applications

Nitric oxide can be used for detecting surface radicals on polymers. Quenching of surface radicals with nitric oxide results in incorporation of nitrogen, which can be quantified by means of X-ray photoelectron spectroscopy.^{[citation needed]}

Biological functions

Main article: Biological functions of nitric oxide

NO is one of the few gaseous signaling molecules known. It is a key vertebrate biological messenger, playing a role in a variety of biological processes. Nitric oxide, known as the 'endothelium-derived relaxing factor', or 'EDRF', is biosynthesised endogenously from arginine and oxygen by various nitric oxide synthase (NOS) enzymes and by reduction of inorganic nitrate. The endothelium (inner lining) of blood vessels use nitric oxide to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increasing blood flow. Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule.^[12] The production of nitric oxide is elevated in populations living at high-altitudes, which helps these people avoid hypoxia by aiding in pulmonary vasculature vasodilation. Effects include vasodilatation, neurotransmission (see gasotransmitters), modulation of the hair cycle, production of reactive nitrogen intermediates and penile erections (through its ability to vasodilate). Nitroglycerin and amyl nitrite serve as vasodilators because they are converted to nitric oxide in the body. Sildenafil citrate, popularly known by the trade name Viagra, stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis.

Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. Humans with atherosclerosis, diabetes, or hypertension often show impaired NO pathways.^[13] A high-salt intake was demonstrated to attenuate NO production, although bioavailability remains unregulated.^[14]

Nitric oxide is also generated by phagocytes (monocytes, macrophages, and neutrophils) as part of the human immune response. Phagocytes are armed with inducible nitric oxide synthase (iNOS), which is activated by interferon-gamma (IFN-γ) as a single signal or by tumor necrosis factor (TNF) along with a second signal.^[15] On the converse, transforming growth factor-beta (TGF-β) provides a strong inhibitory signal to iNOS, whereas interleukin-4 (IL-4) and IL-10 provide weak inhibitory signals. In this way the immune system may regulate the armamentarium of phagocytes that play a role in inflammation and immune responses. Nitric oxide secreted as an immune response is as free radicals and is toxic to bacteria; the mechanism for this includes DNA damage and degradation of iron sulfur centers into iron ions and iron-nitrosyl compounds.^[16][17][18] In response, however, many bacterial pathogens have evolved mechanisms for nitric oxide resistance.^[19] Because nitric oxide might serve as an inflammometer in conditions like asthma, there has been increasing interest in the use of exhaled nitric oxide as a breath test in diseases with airway inflammation.

Nitric oxide can contribute to reperfusion injury when an excessive amount produced during reperfusion (following a period of ischemia) reacts with superoxide to produce the damaging oxidant peroxynitrite. In contrast, inhaled nitric oxide has been shown to help survival and recovery from paraquat poisoning, which produces lung tissue-damaging superoxide and hinders NOS metabolism.

In plants, nitric oxide can be produced by any of four routes: (i) L-arginine-dependent nitric oxide synthase,^[20][21][22] (although the existence of animal NOS homologs in plants is debated),^[23] (ii) by plasma membrane-bound nitrate reductase, (iii) by mitochondrial electron transport chain, or (iv) by non-enzymatic reactions. It is a signaling molecule, acts mainly against oxidative stress and also plays a role in plant pathogen interactions. Treating cut flowers and other plants with nitric oxide has been shown to lengthen the time before wilting.^[24]

An important biological reaction of nitric oxide is S-nitrosylation, the conversion of thiol groups, including cysteine residues in proteins, to form S-nitrosothiols (RSNOs). S-Nitrosylation is a mechanism for dynamic, post-translational regulation of most or all major classes of protein.

Mechanism of action

There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. These include oxidation of iron-containing proteins such as ribonucleotide reductase and aconitase, activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron regulatory factor activation.^[25] NO has been demonstrated to activate NF-κB in peripheral blood mononuclear cells, an important transcription factor in iNOS gene expression in response to inflammation.^[26] It was found that NO acts through the stimulation of the soluble guanylate cyclase, which is a heterodimeric enzyme with subsequent formation of cyclic GMP. Cyclic GMP activates protein kinase G, which caused phosphorylation of myosin light chain phosphatase (and therefore inactivation) of myosin light-chain kinase and leads ultimately to the dephosphorylation of the myosin light chain, causing smooth muscle relaxation.^[27]

Use in pediatric intensive care

Nitric oxide/oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat primary pulmonary hypertension in neonatal patients^[28][29] post meconium aspiration and related to birth defects. These are often a last-resort gas mixture before the use of extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy has the potential to significantly increase the quality of life and, in some cases, save the lives of infants at risk for pulmonary vascular disease.^[30]

Pharmacology

Nitric oxide is considered an anti-anginal drug: it causes vasodilation, which can help with atherosclerosis by improving blood flow to the heart. Nitroglycerin pills, taken sublingually (under the tongue), are used to prevent or treat acute chest pain (ACS). The nitroglycerin reacts with a sulfhydryl group (–SH) to produce nitric oxide, which eases the pain by causing vasodilation.

See also

• Nitrogen
• Nitrous oxide

References

1. ^ Hou Y.C., Janczuk A. and Wang P.G. (1999): Current trends in the development of nitric oxide donors. Curr. Pharm. Des. June, 5 (6): 417–471
2. ^ Tylor B.S., Kion Y.M., Wang Q.I., Sharpio R.A., Billiar T.R. and Geller D.A. (1997): Nitric oxide down regulates hepatocyte-inducible nitric oxide synthase gene expression. Arch. Surg. 1, (32). Nov.; 1177–1182.
3. ^ ^{a b} Elizabeth Culotta and Daniel E. Koshland Jr (December 1992). "NO news is good news. (nitric oxide; includes information about other significant advances & discoveries of 1992) (Molecule of the Year)". Science 258 (5090): 1862–1864. doi:10.1126/science.1361684. PMID 1361684. 
4. ^ Ueber Synthesen stickstoffhaltiger Verbindungen mit Hülfe des Stickoxyds Justus Liebig's Annalen der Chemie Volume 300, Issue 1, Date: 1898, Pages: 81–128 Wilhelm Traube doi:10.1002/jlac.18983000108
5. ^ Nitric Oxide Reacts with Methoxide Frank DeRosa, Larry K. Keefer, and Joseph A. Hrabie J. Org. Chem. 2008, 73, 1139–1142 doi:10.1021/jo7020423
6. ^ Robert H. Crabtree: "The Organometallic Chemistry of the Transition Metals", page 32.
7. ^ Robert H. Crabtree: "The Organometallic Chemistry of the Transition Metals", pages 96-98.
8. ^ Fontijn, A., A. J. Sabadell and R. J. Ronco (1970). "Homogeneous chemiluminescent measurement of nitric oxide with ozone." Analytical Chemistry 42(6): 575–579.
9. ^ Vanin A. F.; Huisman A.; van Faassen E.E.; Methods in Enzymology vol 359 (2002) 27–42
10. ^ Nagano T.; Yoshimura T.; "Bioimaging of nitric oxide", Chemical Reviews vol 102 (2002) 1235–1269.
11. ^ “Production: Growth is the Norm” Chemical and Engineering News, July 1 0, 2006, p. 59.
12. ^ Stryer, Lubert (1995). Biochemistry, 4th Edition. W.H. Freeman and Company. pp. 732. ISBN 0-7167-2009-4. 
13. ^ Dessy, C.; Ferron, O. (September 2004). "Pathophysiological Roles of Nitric Oxide: In the Heart and the Coronary Vasculature". Current Medical Chemistry – Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Bentham Science Publishers Ltd.) 3 (3): 207–216. ISSN 1871–5230. 
14. ^ http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=223997&Ausgabe=228460&ArtikelNr=63555
15. ^ Gorczyniski and Stanely, Clinical Immunology. Landes Bioscience; Austin, TX. ISBN 1570596255
16. ^ Nitric oxide synthesis and TNF-alpha secretion in RAW 264.7 macrophages: mode of action of. 
17. ^ Threshold Effects of Nitric Oxide-Induced Toxicity and Cellular Responses in Wild-Type and p53-Null Human Lymphoblastoid Cells
18. ^ Hibbs JB, Jr., Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94.
19. ^ C. A. Janeway, et al. (2005). Immunobiology: the immune system in health and disease (6th ed. ed.). New York: Garland Science. ISBN 0-8153-4101-6. 
20. ^ Corpas et al. (2004). "Cellular and subcellular localization of endogenous nitric oxide in young and senescent pea plants". Plant Physiology 136 (1): 2722–33. doi:10.1104/pp.104.042812. PMID 15347796. 
21. ^ Corpas et al. (2006). "Constitutive arginine-dependent nitric oxide synthase activity in different organs of pea seedlings during plant development". Planta 224 (2): 246–54. doi:10.1007/s00425-005-0205-9. 
22. ^ Valderrama et al. (2007). "Nitrosative stress in plants". FEBS Lett 581 (3): 453–61. doi:10.1016/j.febslet.2007.01.006. 
23. ^ Corpas et al. (2004). "Enzymatic sources of nitric oxide in plant cells – beyond one protein–one function". New Phytologist 162: 246–7. doi:10.1111/j.1469-8137.2004.01058.x. 
24. ^ Judy Siegel-Itzkovich. Viagra makes flowers stand up straight. Student BMJ, September 1999.
25. ^ Shami P.J., Moore J.O., Cockerman J.P., Halhorn W.J., Misukonis M.A., and Weinberg J.B. (1995): Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukaemia cells. Leukaemia Research; 19(8): 527–534.
26. ^ Kaibori M., Sakitani K., Oda M., Kamiyama Y., Masu Y. and Okumura T.(1999). Immunosuppressant FK56 inhibits iNOS gene expression at a step of NF-Kappa B activation in rat hepatocytes. J. Hepatol. Jan; 30 (6): 1138–1145.
27. ^ 'cGMP-Dependent Protein Kinase I and Smooth Muscle Relaxation: A Tale of Two Isoforms', Howard K. Surks (Circ. Res. 2007;101;1078–1080)
28. ^ Finer NN, Barrington KJ (2006). "Nitric oxide for respiratory failure in infants born at or near term". Cochrane Database Syst Rev (4): CD000399. doi:10.1002/14651858.CD000399.pub2. PMID 17054129. 
29. ^ Chotigeat U, Khorana M, Kanjanapattanakul W (February 2007). "Inhaled nitric oxide in newborns with severe hypoxic respiratory failure". J Med Assoc Thai 90 (2): 266–71. PMID 17375630. 
30. ^ Hayward C.S., Kelly R.P. and Macdonald P.S. (1999): Inhaled nitric oxide in cardiology practice. Cadio. Vasc. Res. Aug.; 15, 43 (3): 628–638.

Further reading

• Butler A. and Nicholson R.; " Life, death and NO." Cambridge 2003. ISBN 978-0-85404-686-7.
• Corpas FJ et al. “Constitutive arginine-dependent nitric oxide synthase activity in different organs of pea seedlings during plant development” Planta 2006 224(2):246–54.
• Corpas FJ, del Río LA, Barroso JB. "Need of biomarkers of nitrosative stress in plants" Trends Plant Sci. 2007 12(10):436–8.
• van Faassen, E. E.; Vanin, A. F. (eds); " Radicals for life: The various forms of Nitric Oxide." Elsevier, Amsterdam 2007. ISBN 978-0-444-52236-8.
• F.A. Cotton, G. Wilkinson, C.A. Murillo, M. Bochmann; Advanced Inorganic Chemistry, 6th ed. Wiley-Interscience, New York, 1999.
• K.J. Gupta , M. Stoimenova, and W. M. Kaiser "In higher plants, only root mitochondria, but not leaf mitochondria reduce nitrite to NO, in vitro and in situ" Journal of Experimental Botany 2005 56(420):2601–2609.
• E.Planchet, K.J. Gupta, M .Sonada & W.M.Kaiser (2005) "Nitric oxide emission from tobacco leaves and cell suspensions: rate limiting factors and evidence for the involvement of mitochondrial electron transport"The Plant Journal 41 (5), 732–743.
• Stöhr, C.; Stremlau, S. "Formation and possible roles of nitric oxide in plant roots" Journal of Experimental Botany 2006 57(3):463–470.
• Pacher, P.; Beckman, J. S.; Liaudet, L.; “Nitric Oxide and Peroxynitrite: in Health and disease” Physiological Reviews 2007, volume 87(1), page 315–424. PMID 17237348.
• Valderrama et al. "Nitrosative stress in plants" FEBS Lett. 2007 581(3):453–61.

External links

• International Chemical Safety Card 1311
• National Pollutant Inventory – Oxides of nitrogen Fact Sheet
• 1998 Nobel Prize in Physiology/Medicine for discovery of NO's role in cardiovascular regulation
• Nitric Oxide and its Role in Diabetes, Wound Healing and Peripheral Neuropathy
• Microscale Gas Chemistry: Experiments with Nitrogen Oxides
• Your Brain Boots Up Like a Computer – new insights about the biological role of nitric oxide.
• Assessing The Potential of Nitric Oxide in the Diabetic Foot
• New Discoveries About Nitric Oxide Can Provide Drugs For Schizophrenia
• Nitric Oxide at the Chemical Database

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