Nitric oxide is a kind ofinorganic compound, chemical formula is NO, which is a kind ofNitrogen oxidesThe valence of nitrogen is+2.Colorless gas under normal temperature and pressure, slightly soluble inwater, soluble inethanol、carbon disulfide。
In 1980, a scientist completed an experiment and published a paper on it.This is not a very important thing, but it is a turning point for nitric oxide, although the scientific community did not know that that particular substance was nitric oxide this year.
The name of this American pharmacologist is Robert F. Fauchegott《natural》A paper published in the journal Nature pointed out that the vasodilation effect of acetylcholine (ACh) depended on certain diffusible substances released by vascular endothelium.Then they found outbradykinin(BK) and other substances also follow a similar mechanism in vasodilation, and this substance is named vascular endothelial relaxing factor (EDRF).
Fauchegott found that there is a substance that can relax blood vessels, which is not unique to him. As early as the 1870s, people found thatOrganic nitrateyesischemic heart diseaseIt has good therapeutic effect, but its mechanism was not understood at that time.At the end of the 19th century, while Nobel was famous for developing high performance explosives (TNT), people were surprised to find thatglyceryl trinitrate(GTN) is the main active component of high performance explosives, which has puzzled people.
Since the discovery of vasodilation is not special, why does Fauchegoth's paper attract the attention of the scientific community?The reason is that he proved the existence of this kind of material with his ingeniously designed experiment.
On the surface, Fauchegoth's research is not directly related to nitric oxide, but about the action mechanism of vasoactive substances such as acetylcholine.In 1953, he published his first paper on the contraction of isolated rabbit vascular strips caused by acetylcholine and histamine, which was contrary to the widely accepted view at that time that intravenous injection of acetylcholine or histamine into whole animals would cause vasodilation.However, he insisted that his experiments were well repeated and his observations were correct. In the review of Pharmacology of Vascular Smooth Muscle published in 1955, he put forward the hypothesis that just like adrenaline can have alpha and beta receptors, vascular smooth muscle also contains both exercise-induced and inhibitory cholinergic receptors - this conclusion is wrong,However, at that time, this view has been recognized as an authority.
The next question is, why can stimulating endothelial cells cause vasodilation of vascular smooth muscle?This seems to be a straightforward approach. What they first thought is that vascular endothelial cells will release certain substances after being stimulated, which will diffuse to smooth muscle and cause it to contract.Fochegoth seemed to be inspired by some special idea. He recalled: "I just woke up that morning, a beautiful experimental design suddenly burst into my mind. So I came to the laboratory and immediately carried out the experiment according to this scheme." The experimental results were written into a paper and published in the journal Nature in 1980,The title of the paper is "Endothelial cells are essential factors for acetylcholine induced relaxation of arterial smooth muscle".
It is worth mentioning that this article in the journal Nature did not explicitly propose endothelium relaxing factor at that time. Until 1982, they formally proposed the term endothelium relaxing factor in their paper on bradykinin endothelium dependent vasodilation published in the Journal of the National Academy of Sciences (PNAS).
This paper has attracted extensive attention in the academic community, and attracted many scientific workers, including Professor Louis J. Ignarro of the University of California, Los Angeles, to engage in research on endothelial relaxing factor.Endothelial relaxing factor is an unstable compound, which can be inactivated by hemoglobin and superoxide anion free radicals.Ignaro, who has been studying the pharmacological effects of nitroso compounds for a long time, cooperated with Fauchegott to carry out a series of experiments on the pharmacological effects and chemical essence of endothelial relaxing factor, and found that endothelial relaxing factor, like nitric oxide and many nitroso compounds, can activate solubilityGuanylate cyclase(SolubleGuanylateCycle, sGC), nitric oxide mainly passesCyclic guanosine(cGMP) pathway dilates blood vessels.
Dr. Murad's discovery
In the 1950s, cyclic guanosine was found in the urine as a natural product marker. Related enzymes include guanylate cyclase (GC), which acts on the synthesis of cyclic guanosine, phosphodiesterase that hydrolyzes cyclic guanosine, and phosphodiesterase that is selectively activated by cyclic guanosineprotein kinase。
After finishing his training at the National Institutes of Health (NIH) in 1970, Dr. Murad decided to transfer more research energy from cyclic adenosine phosphate (cAMP) to cyclic guanosine monophosphate, and tried to solve two problems: first, how do hormone ligands bind with their receptors to regulate guanylate cyclase?Second, what is the molecular coupling event?Understanding of receptor guanylate cyclase coupling is helpful to use preparations or drugs to enhance or inhibit the influence of hormones in some clinical diseases.
At the University of Texas Medical School, Dr. Murad, a pharmacologist who has been independently engaged in the study of the vasodilation effect of nitroglycerin for many years, found that nitroester drugs and exogenous nitric oxide can increase the content of cyclic guanosine as early as 1977,They even suggested that nitroester drugs may increase the content of cyclic guanosine in cells through the formation of nitric oxide or some active substance, thereby expanding blood vessels and inhibiting platelets.So far, many studies have focused on nitro active substances.
As early as the 1970s, Dr. Murad and his collaborators systematically studied the pharmacological effects of nitroglycerin and other organic nitro compounds with the effect of enhancing vascular activity, and found that these compounds can increase the concentration of second messengers such as cyclic guanylic acid and cyclic adenosine monophosphate in tissues.These compounds have a common property that they can metabolize nitric oxide in the body.In 1977, Dr. Murad found that nitroglycerin and other substances must be metabolized into nitric oxide to play the role of vasodilation, so he thought that nitric oxide may be a messenger molecule that can regulate blood circulation, but at that time, there was no experimental evidence for this inference.
In his previous work, Dr. Murad found that the activity of guanylate cyclase can be detected in different tissue homogenates (including high-speed centrifugation supernatant and homogenate particles).However, in the two tissue preparations, the kinetic characteristics of enzyme activity are different. The most significant feature is that the homogenate particles show a synergetic catalytic kinetics on the activity of the matrix guanosine triphosphate (GTP), while the activity of soluble guanylate cyclase is confirmed to be a typical Mieman's kinetics, which suggests that the activity of soluble guanylate cyclase represents aGuanosine triphosphateThe catalytic site of.Although it is speculated that guanylate cyclase has different subtypes, the crude product also contains competitive substrates or productsNucleotidase、phosphataseandphosphodiesteraseUnable to eliminate unreliable false data, Murad spent a full 12 years purifying, validating, cloning, expressing and re validating this enzyme to completely solve this problem.
Through experiments, Dr. Murad found that certain substances, including sodium azide, nitrite and hydroxylamine, can activate guanylate cyclase.In different tissues including tracheal smooth muscle preparations,Sodium azide、nitriteandhydroxylamineIt can also increase the level of cyclic guanosine.The increase of these cyclic guanosine levels is related to the relaxation of smooth muscle, showing a linear dose response relationship.Nitroglycerin, a drug used in clinical angina since the 1870s, can also activate soluble guanylate cyclase, increase the level of cyclic guanosine in different tissues, including tracheal smooth muscle, and cause smooth muscle relaxation.
Dr. Murad said that the relaxants of tracheal, gastrointestinal and vascular smooth muscle in the growing list of soluble guanylate cyclase activators were "nitrovasodilators", and he was sure that they could be converted into nitric oxide, because the nitric oxide produced by chemical method could activate all the soluble guanylate cyclase preparations in the test.The mechanism of action of these nitric oxide prodrugs is therefore determined.
Dr. Murad proposed the hypothesis that nitric oxide can play a role in regulating intracellular messengers of hormones and drugs, that is, a free radical activates an enzyme, and this free radical is an endogenous messenger molecule.Due to the activation of purified soluble guanylate cyclaseNamolIn the seven or eight years after the development of the new technology for the analysis and determination of nitric oxide, this hypothesis, which was doubted by the academic circles in that year, was finally confirmed and accepted because the determination of nitric oxide and its oxidation products, nitrite and nitrate, were insensitive.
Dr. Murad said that there are two sources of nitric oxide in the human body: one is non enzymatic, which comes from the chemical degradation and transformation of inorganic nitrogen on the body surface or ingested;One is enzymatic, catalyzed by nitric oxide synthaseL-ArginineIt is produced by deguanidine.Non enzymatic nitric oxide, mostly from the family of nitrovasodilators, including nitroprusside, organic or inorganicnitriteandNitrate、Nitrosamine、Nitrogen mustard、HydrazineEtc.For example, famousglyceryl trinitrateandsodium nitroprussideThe function of vasodilation and treatment of heart disease is through the non enzymatic production of nitric oxide.Enzymatic nitric oxide is derived from the precursor of nitric oxide, such as arginine.Ingestion of richArginineIn the body, nitric oxide is produced enzymatically and plays its physiological function.
Mechanism of enzymatic nitric oxide production (L-arginine is produced under the action of endothelial nitric oxide synthaseL-citrullineAnd release nitric oxide)
Dr. Murad's research focuses on the effect of non enzymatic nitric oxide compounds onNitric oxide synthaseThis not only clarifies the mechanism of nitric oxide in vasodilation in vivo, but also opens the way for the research and development of new drugs and cosmetics.The technology applied by the biotechnology company Dr. Murad is a combination that can produce nitric oxide, which is nitrogen agent and acid agent, in which nitrogen agent is nitrite or plant extract rich in nitrite, and acid agent is organic or inorganic acid with sufficient strength such as vitamin C and citric acid.When using, first clean the skin, apply an appropriate amount of nitrogen cosmetics, and then apply acid cosmetics. The two slowly react to release nitric oxide, penetrate into the skin, increase capillary blood flow, promote collagen synthesis, and improve the skin texture.
It is worth mentioning that as early as the end of the 19th century, German scholar Griess studied and published the detection method of nitrite, but did not understand its relationship with nitric oxide at that time.Since nitrite is the end product of nitric oxide oxidation metabolism in aqueous solution and is relatively stable, the modified Griess method is still one of the simplest and most commonly used methods for indirect detection of nitric oxide content in the laboratory.
Study on nitric oxide and nucleic acid
In the 1980s, the world life science field established the theory of "three messengers transmitting life information", that is, various activities of life bodies are controlled and regulated by the three messenger systems.
We all know protein and nucleic acidBiomacromoleculeIt is the main embodiment of life, but not life itself.The essence of life is the complex and orderly interaction between these biological macromolecules, which is the basic task of information transmission research.
The essence of life information transmission is extracellular communication between cellsFirst MessengerAnd the outside worldenvironmental factor After acting on cell surface or intracellular receptorsTransmembrane transportIntracellular formationSecond MessengerCascading transmission of, and subsequent intranuclearThird Messengerinducegene expressionAnd the process of causing physiological reaction.While responding to environmental stimuli and regulating gene expression and physiological responses, life information transmission not only maintains normal cell metabolism, but also ultimately determines the basic phenomena of life such as cell proliferation, growth, differentiation, aging and death.
Three messengers delivering life information
First MessengerIt refers to all kinds of extracellularInformation molecule, also known as intercellularSignal moleculeCytokines, such as endocrine hormones, prostaglandins, gas signaling molecules (NO) andImmune cellProduced immune cytokines.After these bioactive molecules are produced by various cells in the body, they can act on the surface of cell membrane through different ways such as blood, lymph, and various body fluids, causing specific reactions in cells.
Second MessengerIt means that after the first extracellular messenger combines with its specific receptorInformation transmembrane transmissionMechanism activated receptors stimulate specific effector enzymes or ion channels in the cell membrane and produce messenger substances in the cytoplasm.This intracellular information molecule plays the role of transmitting, amplifying and transforming extracellular information into recognizable information in cells.
Third Messengeralso calledDNA Binding ProteinIt refers to the substance responsible for the transmission of information outside the nucleus, which canRegulatory geneTranscriptional level, playtranscription factorRole of.These proteins are synthesized in the cytoplasm of the cell and enter the nucleus to play the role of messenger, so they are called "the third messenger in the nucleus".
Therefore, nucleic acid is a substance with genetic function in cells, and NO is a communication substance between cells. Without NO, no number of cells can work together and interact with each other. It is meaningless that life information cannot be transmitted. Only when the two are organically combined can they jointly undertake the task of human metabolism.
Material structure
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Nitric oxide is a diatomic molecule with a linear molecular configuration.In nitric oxide, a σ bond, a 2-electron π bond and a 3-electron π bond are formed between nitrogen and oxygen.The bond order between nitrogen and oxygen is 2.5, and there is a pair of lone electrons for each of nitrogen and oxygen.There are 11 valence electrons, which are odd electron molecules with paramagnetism.On the antibonding orbital (πtwoP *) 1 It is easy to lose the formation of nitrite cation NO.
Physical and chemical properties
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physical property
Melting point: - 163.6 ℃
Boiling point: - 151.8 ℃
Density: 1.27kg/mthree
Saturated vapor pressure: 6079.2 kPa (- 94.8 ℃)
Appearance: colorless gas
Solubility: slightly soluble in water, soluble in ethanol, carbon disulfide
chemical property
Nitric oxide is a colorless gas, which is prepared by using air on platinum mesh catalystAmmoxidationMethods;In the laboratory, copper andDilute nitric acidReaction.
The solubility of NO in water is small, and it does not react with water.Under normal temperature, NO is easily oxidized to nitrogen dioxide, and can also react with halogen to produce halogenated nitrosyl (NOx）。E.g. 2NO+Cltwo=2NOCl
But NO and OtwoIt can react with water, and the chemical equation is 4NO+3Otwo+2HtwoO=4HNOthree
According to the molecular structure of NO, it has unpaired electrons. Two atoms have 11 valence electrons in total, that is, an odd molecule. Most odd molecules have color. However, NO is only blue in liquid or solid state.NO molecules in solid state will form relaxed dimers (NO)twoThis is also the inevitable result of its single electron.
It should be noted here that NO can be absorbed by sodium peroxide: NatwoOtwo+2NO=2NaNOtwo[2]
Calculate chemical data
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Reference value for drainage parameter calculation (XlogP): 0.2[5]
Number of hydrogen bond donors: 0[5]
Number of hydrogen bond receptors: 1[5]
Number of rotatable chemical bonds: 0[5]
Number of tautomers: none
Topological molecular polar surface area: 18.1[5]
Number of heavy atoms: 2[5]
Surface charge: 0[5]
Complexity: 2[5]
Number of isotope atoms: 0[5]
Determine the number of atomic structure centers: 0[5]
Number of uncertain atomic structure centers: 0[5]
Determine the number of chemical bond structure centers: 0[5]
Number of uncertain chemical bond structure centers: 0[5]
Number of covalent bond units: 1[1]
toxicology data
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1. Acute toxicity data
Rats inhaled LCfifty：1068 mg/mthree/4h
Mice inhaled LCLo: 320ppm
LCLo inhaled by mammals and dogs: 5000 ppm/25M
2. Other multi dose data
Rats inhaled TCLo: 50 mg/mthree/6H/7W-I
Rats inhaled TCLo: 3 mg/mthree/24H/16D-C
TCLo inhaled by mice: 10 ppm/2H/30W-I
3. Mutagenic data
Bacteria Salmonella typhimurium: 30 ppm.
Rats inhaled 27 ppm/3H (continuous) mutations in mammalian somatic cells.
Rodent hamster fibroblast 10 ppm mutation in mammalian somatic cells.
4. It is a blood poison, which turns oxygenated hemoglobin into denatured hemoglobin and causes cyanosis, resulting in paralysis and spasm of the brain.In case of mild poisoning, the symptoms may disappear after being moved to fresh air.As nitric oxide quickly turns into nitrogen dioxide in the air, the latter is also toxic to human body, stimulating and corrosive to lung tissue, causing pulmonary edema.Chronic effects are mainly manifested as neurasthenic syndrome and chronic respiratory inflammation.Pulmonary fibrosis occurred in individual cases.In addition, tooth erosion can also occur.
5. Nitric oxide can cause central nerve paralysis and spasm.When people absorb nitric oxide, it will rapidly oxidize into toxic nitrogen dioxide.The symptoms of poisoning are the same as that of nitrogen dioxide.The maximum allowable concentration of nitric oxide in the air (converted into nitrogen dioxide) is 0.15mg/m in residential areathree5mg/m in the workplacethree[1]
application area
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clinical application
NO is a gas at room temperature, and its fat solubility is one of the possible factors that make it become a messenger molecule in the human body.It can quickly diffuse through the biofilm without any intermediary mechanism, and transmit the information generated by a cell to the cells around it. The main influencing factor is its biological half-life.It is characterized by a variety of biological functions because it is a free radical, which is very easy to participate in and transfer electron reactions and participate in the redox process of the body.The molecular coordination makes it have high affinity with heme iron and non heme iron to replace OtwoAnd COtwoLocation of.According to research reports, hemoglobin NO can lose its nearby base and become free protoheme NO, which means that free base can freely participate in catalytic reaction, free protein can freely change conformation, free heme can freely diffuse out of protein, any one of the three changes or their combination,Will play an important role in the activation of guanylate cyclase[3]。The research on the biological function and mechanism of NO is in the ascendant, and its discovery indicates the prospect of inorganic molecules in the medical field.
Nitric oxide acts as a messenger molecule.When the endothelium sends a relaxation command to the muscle to promote blood circulation, it will produce some nitric oxide molecules, which are very small and can easily pass through the cell membrane.The smooth muscle cells around the blood vessels relax after receiving the signal, making the blood vessels dilate.
Role in urinary and reproductive system
Nitric oxide, as a neurotransmitter of NANC, plays an important role in the genitourinary system and becomes a regulator of physiological functions such as urinary continence, which provides a theoretical basis for drug treatment of genitourinary diseases.
It has been proved that the nervous system with NO as the transmitter widely exists in the human body, which is as important as adrenergic nerve, cholinergic nerve and peptide nerve.If its function is abnormal, it may cause a series of diseases.
Role in the nervous system
Studies on the L-Arg → NO pathway in the central nervous system (CNS) suggest that NO acts on adjacent peripheral neurons, such as prominent anterior nerve endings and astrocytes, through diffusion, and reactivates GC to increase the level of cGMP and produce physiological effects.For example, NO can induce the long-term potentiation (LTP) related to learning and memory, and plays a reverse messenger role in its LTP.
Continuous stimulation of the ascending and parallel fibers of the cerebellum can cause long term depression (LTD) of nerve conduction of parallel fiber cells, which is considered as a mechanism in cerebellar motor learning system, and NO participates in this mechanism.
L-Arg → NO pathway also exists in the peripheral nervous system.NO is considered to be the transmitter or medium of non cholinergic and non adrenergic nerves, and participates in the process of pain afferent and sensory transmission.
NO plays an important mediating role in gastrointestinal nerve mediated relaxation of gastrointestinal smooth muscle. In the gastrointestinal nerve plexus, NOS and vasoactive intestinal peptide coexist and can cause nonadrenergic non cholinergic (NANC) relaxation, but the vasoactive intestinal peptide antagonist can only partially eliminate the relaxation of NANC, and the rest of the relaxation reaction can be eliminated by N-methylarginine.
Role in the immune system
The results show that NO can be produced in a variety of cells in the human body.For example, when endotoxin or T cells in the body activate macrophages and polymorphonuclear leukocytes, they can produce a large number of inducible NOS and superoxide anion free radicals, thus synthesizing a large number of NO and HtwoOtwo, which plays a very important role in killing invading bacteria, fungi and other microorganisms, tumor cells, organic foreign bodies and inflammatory damage.
It is currently believed that NO released by activated macrophages can kill target cells by inhibiting the tricarboxylic acid cycle in the mitochondria of target cells, electron transfer cell DNA synthesis and other pathways.
The NO produced by immune reaction also has toxic effects on adjacent tissues and cells that can produce NOS.Some local or systemic tissue damage related to the immune system, abnormal expansion and permeability of blood vessels and lymphatic vessels, etc., may be closely related to the content of NO in the local.
Action mechanism of cardio cerebral vessels
Nitric oxide is a compound of nitrogen, chemical formula NO, molecular weight 30, and the valence of nitrogen is+2.Nitric oxide has free radicals, which makes its chemical properties very active.It has paramagnetism.When it reacts with oxygen, it can form a corrosive gas - nitrogen dioxide (NOtwo）。Nitric oxide is a colorless gas under standard conditions, and the liquid and solid are blue.The mechanism of nitric oxide improving cardiovascular and cerebrovascular function.
The production of nitric oxide can be roughly divided into two types, one is enzymatic nitric oxide, and the other is non enzymatic nitric oxide.
Non enzymatic is generated through donor generation of clinical drugs such as nitroglycerin and nitroprusside.Enzymatic properties must involve enzymes, as well asPrecursor substancesOf.This enzyme is called nitric oxide synthase (NOS). There are three such enzymes in the human body, which are divided into endothelial nitric oxide synthase and distributed in vascular endothelial cells;Neurotype nitric oxide synthase, distributed in human neuron cells;The last one is called inducible nitric oxide synthase, which is distributed in the human bodyImmune cellSuch as lymph and T cells.
Fig. 1 Nitric oxide synthesis mechanism
Among them, an endothelial nitric oxide synthase (NOSS), an enzyme extracted from marine organisms, has a higher activity, which can enhance the nitric oxide circulation mechanism in the body and continuously produce nitrous oxide.However, this enzyme is rare and must be made of marine organismsJianhailong、Oysters、ProtamineAnd other precious marine species can be extracted and produced.The synthesis formula of enzymatic nitric oxide isL-Arginine+ NOS + Otwo= NO +L-citrullineCitrulline can generate arginine through a series of chemical reactions.See Figure 1 for details:
Arginine conversion mechanism
Nitric oxide gas produced in vascular endothelial cells, because it isLiposolubilitySo it quickly permeates the cell membrane and diffuses downward intosmooth muscle cell, so as to act on smooth muscle cells, relax them, expand blood vessels, and finally lead to the decline of blood pressure!At the same time, it will also quickly penetrate the cell membrane and spread upward into the blood, enter the platelet cells, reduce the platelet activity, inhibit its agglutination and adhesion to the vascular endothelium, thus preventing the formation of thrombus and the occurrence of atherosclerosis.Biochemically speaking, nitric oxide is a free radical gas, which carries an unpaired electron and is extremely unstable in the body, just like other free radicals.In this way, the two can easily combine to produce reaction.Thus, the number of free radicals in the body is greatly reduced.Due to the synthesis of nitric oxide itselfNitric oxide synthase(NOS), but normally the activity of NOS is very low, requiring the activation of nitro drugs or saponin active substances.Therefore, the best production effect of nitric oxide is to cooperate with ginsenosides.
Nitric oxide and human function
Nitric oxide is widely distributed in various tissues of organisms, especially in neural tissues.It is a new type of biological messenger molecule and was selected as a star molecule by American Science magazine in 1992.NO is an extremely unstable biological free radical with small molecule and simple structure. It is a gas at normal temperature, slightly soluble in water, fat soluble, and can quickly diffuse through the biofilm. The biological half-life is only 3-5 s. Its production depends on nitrous oxide synthase and plays a very important biological role in heart, cerebrovascular regulation, nerve, immune regulation, etc.Therefore, people attach great importance to it.
Discovery of NO biological activity
Medical knowledge tells us that there are two important substances that act on vascular smooth muscle:Norepinephrineandacetylcholine。Norepinephrine constricts vascular smooth muscle cells by acting on their receptors.How acetylcholine acts on vascular smooth muscle to relax is still unclear, and the medical community is committed to studying it together.
In 1980, American scientist Furchgott found a small molecule substance in a study that can relax vascular smooth muscle. Later, it was named vascular endothelial derived relaxing factor (EDRF), which is an unstable biological free radical.And enter adjacent smooth muscle cells. In smooth muscle cells, EDRF activates guanylate cyclase, leading tocGMPLevel rise, cGMP activationPKG, relaxing smooth muscle, however, EDRF was identified as NO.as everyone knows,glyceryl trinitrateIt is a drug for treating cardiac pain. For many years, people have been hoping to understand its therapeutic mechanism at the molecular level.It was found that nitroglycerin and other organic compoundsNitrateThey have no activity in themselves. They are first converted into NO in vivo. It is NO that stimulates the formation of cGMP in vascular smooth muscle to dilate blood vessels. This effect is just similar to EDRF.In 1987, Moncada et al., while observing the relaxing effect of EDRF on vascular smooth muscle, determined the substance released by endothelial cells as NO by chemical method, and explained the degree of its relaxation on vascular smooth muscle according to its content.In 1988, Polmer et al. proved that L-arginine is the precursor for vascular endothelial cells to synthesize NO, and the product isCitrullineAnd NO, the process is catalyzed by NO synthase, thus establishing the concept that NO can be synthesized in mammals.[4]
Safety measures
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Environmental hazards
Hazardous characteristics: strong oxidizing.It is easy to ignite and burn in contact with combustibles and organics.Encounter explosive combination of hydrogen.Contact with the air will emit brown and acid oxidizing brown yellow fog.Nitric oxide is less active, but it is easily oxidized into nitrogen dioxide in the air, which is highly corrosive and toxic.
The product is unstable and quickly turns into nitrogen dioxide in the air to produce irritation.Nitrogen oxides mainly damage the respiratory tract.At the initial stage of inhalation, there are only mild eye and respiratory tract irritation symptoms, such as throat discomfort, dry cough, etc.Delayed pulmonary edema, adult respiratory distress syndrome, chest tightness, respiratory distress, cough, cough, foamy sputum and cyanosis often occur after several hours to more than ten hours or a longer incubation period.Pneumothorax and mediastinal emphysema may be complicated.Delayed obstructive bronchiolitis may occur about two weeks after pulmonary edema subsides.High concentration of nitric oxide can cause methemoglobinemia.Chronic effects: mainly manifested as neurasthenic syndrome and chronic respiratory inflammation.Pulmonary fibrosis occurred in individual cases.May cause tooth erosion.
Environmental hazard: It is harmful to the environment and can cause pollution to water, soil and atmosphere.
Flammability hazard: This product supports combustion and is irritant.
Health hazards
Nitric oxide is the culprit of astronaut syncope
The excessive production of nitric oxide will dilate blood vessels, which can explain why astronauts will have syncope after space flight, as well as many similar phenomena on land.
This microgravity phenomenon experienced by astronauts in space is very similar to the feeling that astronauts in space or patients who have been lying in bed for a long time are about to get up. At this time, people will produce too much vasodilator - nitric oxide, which will lead to lower blood pressure, less blood flow to the head, and syncope.
In the experiment on rats, researchers from the University of California found that under the low gravity environment, the two enzymes that produce nitric oxide in rats increased, and when rats were given drugs to inhibit one of these enzymes, their blood pressure increased, which gave researchers a hint: inhibiting nitrous oxide was an effective treatment for syncope in astronauts and long-term bedridden patients.The study was published in the July issue of the journal Practical Physiology.
In our normal upright life, gravity makes blood flow to the lower limbs, so the blood vessels at the lower part of the body contract to ensure that there is enough blood flow in the opposite direction.In the low gravity environment, the blood pressure of the whole body is the same. When astronauts return to the earth, the blood pressure of the head drops sharply due to the excessively dilated blood vessels in the lower part of their bodies, so they will inevitably faint when standing.
People see astronauts walk with great strides after landing because they wear pressurized clothes and can maintain healthy blood pressure.However, their clothes can only be worn for so long, and it will take some time to adapt to gravity.
The researchers said: "The condition of patients who have been in bed for a long time is similar to that of astronauts. It seems that they are not affected by gravity. Therefore, they will faint when trying to stand."
Protective measures
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Engineering control: strictly sealed, providing sufficient local ventilation and overall ventilation.Provide safety shower and eyewash equipment.
Respiratory system protection: wear a self-priming filter gas mask (half mask) when the concentration in the air exceeds the standard.In case of emergency rescue or evacuation, it is recommended to wear an air respirator.
Eye protection: wear chemical safety goggles.
Body protection: penetrating gas type anti-virus clothing.
Hand protection: wear chemical resistant gloves.
Other protection: smoking, eating and drinking are prohibited at the work site.Keep good hygiene habits.
Leakage emergency treatment
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Evacuate the personnel in the leakage contaminated area to the windward place quickly, isolate them for 150m immediately, and strictly restrict access.It is recommended that emergency personnel wear self-contained positive pressure respirators and anti poison clothing.Cut off the leakage source as much as possible.Reasonable ventilation to accelerate diffusion.Dilute and dissolve with spray water.Build a dike or dig a pit to collect a large amount of wastewater generated.Leaking containers shall be properly treated, repaired and inspected before reuse.
Operation, disposal, storage and transportation
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Precautions for operation: it shall be strictly sealed, and sufficient local exhaust and general ventilation shall be provided.Operators must be specially trained and strictly abide by the operating procedures.It is recommended that operators wear self-priming filter gas masks (half masks), chemical safety goggles, gas permeable gas suits, and chemical gloves.Keep away from kindling and heat sources, and smoking is strictly prohibited in the workplace.Keep away from flammable and combustible materials.Prevent gas leakage into the air of the workplace.Avoid contact with halogen.The cylinder and accessories shall be handled with care to prevent damage.Fire fighting equipment and leakage emergency treatment equipment of corresponding types and quantities shall be provided.
Precautions for storage: store in a cool and ventilated warehouse.Keep away from kindling and heat sources.The warehouse temperature should not exceed 30 ℃.It shall be stored separately from combustibles, halogens and edible chemicals, and mixed storage is strictly prohibited.The storage area shall be equipped with leakage emergency treatment equipment.
Transportation precautions: the railway transportation must be reported to the railway bureau for trial operation, and the trial operation period is two years.After the test run, a test run report shall be written and submitted to the Ministry of Railways to officially announce the transportation conditions.When steel cylinders are used for transportation, safety helmets on steel cylinders must be worn.Cylinders are generally placed horizontally, and the mouth of the cylinder should be in the same direction, not crossed;The height shall not exceed the protective fence of the vehicle, and shall be firmly clamped with triangular wood pad to prevent rolling.It is strictly prohibited to mix with combustibles or combustibles, halogens, edible chemicals, etc.Transport in the morning and evening in summer to prevent sunlight exposure.Road transportation shall be carried out according to the specified route, and it is forbidden to stay in residential areas and densely populated areas.It is forbidden to slip during railway transportation.
security information
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Safety terminology
S17：Keep away from combustible material.
Keep away from combustible materials.
S23：Do not breathe gas/fumes/vapour/spray.
Do not breathe gas/smoke/vapor/spray.
S36/37/39：Wear suitable protective clothing, gloves and eye/face protection.
Wear appropriate protective clothing, gloves and eye/face protection.
S45：In case of accident or if you feel unwell, seek medical advice immediately (show the lable where possible).
In case of an accident or feeling unwell, seek medical advice immediately (show the label if possible).
Risk terminology
R8：Contact with combustible material may cause fire.
Contact with combustible materials may cause fire.
Related research
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At the beginning of the outbreak of the global COVID-19 epidemic in 2020, the FDA of the United States approved the expanded access emergency use of inhaled nitric oxide medical devices for the treatment of COVID-19 patients.Immediately, a large number of clinical studies focused on the anti neocoronal mechanism of nitric oxide and the actual clinical effect.
