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WHY NO (Nitric oxide) is important for you?


WHY NO(Nitric oxide) is important for you?

Due to academical interest  towards the exercise physiology, I have observed that people are generally not aware of the NO’s physiological importance. Often people are confused and misinterpret Nitric Oxide(NO) as Nitrous Oxide (NO2) aka,. Laughing gas. In this article you will know about it’s history, important functions, current literature and supplementation.
NO is a gas which consists of only one atom of nitrogen and one of oxygen. It was first discovered by the English Scientist Joseph Priestly in 1772, he discovered some 10 gases in his life time. He was awarded with prestigious Copley medal in 1773. Nitric oxide is one of the important chemical messenger molecule in our body, produced by endothelium cells, which plays an important role in relaxing the smooth muscles. It is synthesized by L-arginine in our body. This reaction is catalyzed by the family of Nitric Oxide Synthases:

 1. Endothelial NOS [eNOS]  -   (helps in smooth muscle relaxation)

2. Neural NOS [nNOS] -    (found in both central and peripheral nerves acts as neurotransmitter)

3. NOS isoform [iNOS]   -   (produced and possible promoter in response to inflammation).



If you want to learn the molecular biology or you can skip it,
The process starts from the binding of acetylcholine from the endothelial cells causes a cascade of reaction which leads to release of calcium ions which then binds to their calcium protein called calmodulin (calcium modulated protein) which activates nitric oxide synthase that catalyzes the reaction of arginine into nitric oxide and citrulline molecule. Then, the nitric oxide gets diffused from endothelial cells to the smooth muscle cells. In smooth muscles, the nitric oxide combines with the Guanylyl Cyclase activates it and then converts the GTP(Guanosine Tri-phosphate) form to cyclic GMP(Guanosine monophosphate) form  that facilitates the dephosphorylation of the Myosin lighted chains which results in smooth muscle relaxation.


Functions of NO :
   1.       Cardiovascular functions: As it has been already discussed that, how NO plays an important role in relaxing the smooth muscles. The secretion of nitric oxide is more in arteries than in veins. Both flow experience a sheer resistance which leads to release in NO.
   2.       Platelet function regulation: The NO produced into the endothelium tissues diffuses into the platelets which than starts the platelet guanylate cyclase that leads to reduction of calcium ions and adhesion to the collagen fibers. In simple words it also acts as a negative feedback and stops the platelet in blood clotting.
   3.       Neural Function: Many studies have supported the role of NO as a neurotransmitter. Nitric oxide synthase has a presence in all the areas of the brain, mainly in the hippocampus and the cerebellum. It is generally suggested that NO may act as a “retrograde messenger”.
   4.       Endocrine Function: Due to its presence in brain’s medulla region it is suggested that NO may act as an important factor because steroid and hormones are synthesis  and secretion depends on the cyclic GMP.
   5.       Immunological function: Microphages activated by the endotoxins releases nitric oxide synthase and are responsible for the release of NO. High concentrations of NO leads to impairment of mitochondria function and damage DNA. The inflammatory response of NO is already discussed  and role in platelet function.

Many studies have shown the nitric oxide as an important mediator in several cardiovascular disorders such as subarachnoid hemorrhage which leads to cerebral vasospasm, the lysid blood cells inhibits the endothelial nitric oxide causing platelets aggregation and clotting. Damage to the coronary endothelium cells also leads to vasospasm. The sensitivity of the NO can be understand by that Hypoxia also reduces the endothelium nitric oxide production and leads to hypoxic vasoconstriction. During cerebrovascular accident may overstimulate neurons containing nitro oxide synthase and may release toxic amount of nitroc oxide in the brain.

Benefits of nitric oxide for humans:
   1.       Two common Nitric oxide supplements are L-arginine and L-citrulline (not covering them as a separate article will be published) both can be obtained also from the natural food sources such as meat, dairy products, legumes and watermelon.
   2.       NO supplementation also helps in the treatment of erectile dysfunction by vasodilation around corporal cavernosal muscle tissue which leads to vasodilation and better blood flow to the penis resulting in better erection.
   3.       People with severe hypertension are also benefitted by NO due to the relaxation of blood vessels and smooth muscles (cardiac muscles). It is also helpful in high blood pressure during the pregnancy, however doctor recommendation must be taken before consuming it.
   4.      There are also many speculations all over the scientific community that NO supplements helps in increasing human athletic performance.
   5.       In current time, scientists are researching on the benefits of NO on diseases like Alzheimer which are related to the brain because of its ability to passing information between cells without any need of synapse.
     
     Excess dosage of NO
   1.       Excess dosage of NO can lead to many problems and dysfunctions in our respiratory system such as collapsing of  alveolus and many other problems.
   2.       It can also leads to many hematological side effects such as methemoglobinaemia (a condition in which the haemoglobin is oxidized or in the ferric state)
   3.       People with hypotension should avoid, it can create a life threatening situation for them.
   4.       Excess NO supplement can also cause diarrhea and vomiting.


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