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Author: Dr Sharnika Abeyakirthi, Dermatologist, Columbo, Sri Lanka, 2009. Revised October 2020.
Nitric oxide is a small gaseous molecule also known as nitrogen monoxide, with the chemical formula NO.
Nitric oxide molecule is synthesised from molecular nitrogen and oxygen at very high temperatures of >10000C. This occurs naturally in the environment during lightning.
In the laboratory nitric oxide can be produced by reduction of nitric acid or nitrous acid. Nitric oxide has a melting point of -163.6°C (109.6 K) and a boiling point of -151.7°C (121.4 K).
Nitric oxide is called a free radical because it contains single unpaired electrons in its molecule. Hence it is reactive, and has a half-life of only a few seconds.
It is considered as an air pollutant responsible for the depletion of the ozone layer. Nitric oxide reacts with oxygen (O2) and ozone (O3) to form nitrogen dioxide (NO2), a brown fume and an environmental pollutant. Nitric oxide generated from automobile engines, industries and power plants is the cause of acid rain and smog.
However, this toxic environmental pollutant has also been shown to be a very important signalling molecule in living organisms including the human body.
Some of the known functions of nitric oxide are listed in the table below.
Nitric oxide controls cutaneous microcirculation. Nitric oxide:
Nitric oxide has shown antimicrobial properties against micro-organisms.
Nitric oxide also plays an important role in T-cell mediated diseases of the skin, and it has both pro and anti-apoptotic properties depending on its concentration, cell type, and availability of other substrates.
Humans produce nitric oxide by several mechanisms.
Nitric oxide synthase has 3 isoforms:
Neuronal NOS and endothelial NOS are constitutive enzymes. Their levels are relatively steady in the human body. They are found in endothelial cells, neurones, skeletal muscles, epithelial cells and many other tissues.
NOS II is inducible and stimulated by specific cytokines. Most cells in the human body synthesise iNOS in response to inflammatory conditions.
As all 3 isoforms of NOS are present either in the epidermal cells, dermal cells or both, skin can produce nitric oxide by an enzyme dependent mechanism.
Human skin can release nitric oxide in an enzyme independent manner by UVA photolysis of nitric oxide stores.
Nitric oxide is also produced by reduction of sweat nitrate by skin commensal bacteria, in particular Staphylococci.
Nitric oxide does not usually exist in its free form in the body due to its unstable nature but reacts with other molecules to form more stable products.
Nitrate is the main storage form of nitric oxide. It is very stable when compared with other storage forms such as nitrites and RSNOs, which are important carriers and donor molecules of nitric oxide.
There are no tests for nitric oxide itself, as it is too unstable. Instead, nitrates, nitrites and nitrosylated compounds may be measured using the following tests.
Deficiency of nitric oxide is suspected to have a role in several disorders.
In the skin, insufficient nitric oxide may result in psoriasis by promoting cell proliferation and reducing differentiation of skin cells.
Consuming food rich in nitrates and nitrites increases the level of nitric oxide and its storage form. Just as deficiency of nitric oxide can lead to disease, too much can also cause disease.
Nitric oxide is released from the cerebral vasculature, brain tissue and nerve endings.
Nitric oxide produced by β cells in the pancreas may damage the cells (apoptosis) causing type 1 diabetes.
In the skin, ultraviolet irradiation may lead to excessive nitric oxide production by enzyme-dependent and independent mechanisms. Nitric oxide has a role in the promotion and growth of melanoma via multiple mechanisms.
Due to its antimicrobial properties, a nitric oxide-releasing gel formulation, berdazimer sodium (SB206, SB207, Novan), is under evaluation to treat dermatophyte fungal infections such as tinea pedis and viral skin infections including genital warts and molluscum contagiosum.
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