Nitric oxide was first identified as a gas by Joseph Priestly in 1772 and is a simple molecule consisting of just one atom of oxygen and one atom of nitrogen. For much of the time since this discovery NO has been thought of simply as an atmospheric pollutant. Nitric Oxide was the first gas discovered to play a biological role in humans and this discovery won the Nobel Prize for Medicine in 1998. In the 1980's researchers were investigating how blood vessels dilate (or relax). Dilation of blood vessels, also known as vasodilation, is extremely important for controlling blood pressure as dilated blood vessels have a larger diameter which allows blood to flow with lower pressure. Conversely, constriction of blood vessels narrows their diameter and increases blood pressure.

At the time drugs such as nitroglycerin were given to patients for heart conditions like angina in order to promote vasodilation and reduce blood pressure, but no-one knew how these drugs worked. In 1980 Robert Furchgott investigated the role of a drug called acetylcholine on vasodilation and found that relaxation of blood vessels only occurred if a special class of cells called endothelial cells were present. Endothelial cells are the cells that line the insides of blood vessels and are in direct contact with the blood (see animation below). Behind the endothelial cells are another specialised type of cell known as smooth muscle cells. The contraction and relaxation of these muscle cells is thought to be responsible for constricting or dilating the blood vessels.

Robert Furchgott and his group found that without the endothelial cells the smooth muscle cells were not able to cause vasodilation. This suggested that there was some kind of factor produced by the endothelial cells that was required for relaxation of the blood vessels. This factor was termed Endothelial Derived Relaxing Factor or EDRF and the search to find and identify EDRF began.

Independently, in 1977 Ferid Murad was investigating how nitroglycerin works and discovered that it can release nitric oxide which in turn was able to cause relaxation of smooth muscle cells.

The pieces of the puzzle were finally put together in 1986 when Louis Ignarro identified EDRF and found that it had identical properties to the gas nitric oxide. This was the first time that a gas had been shown to play an important role in regulating biological functions in humans. For their role in this discovery Furchgott, Murad and Ignarro were awarded the Nobel Prize for Medicine or Physiology in 1998.

Since the discovery of this role for nitric oxide it has been shown to be involved in a large number of other roles including cell migration and apoptosis. It has also been shown to be important in a wide variety of different species from plants, to insects and mammals. Only a small number of other gases have been shown to play a role in mammalian cells. These are carbon monoxide and hydrogen sulphide, although these two gases appear to have far fewer role than nitric oxide.

You can read more about the biological roles of NO here.

Nitric Oxide	Role in biology	Synthesis
Regulation	cGMP	Nitrosylation