Nitric oxide in our bodies

Nitric oxide has the formula NO. It is a colourless gas at room temperature and pressure, and consists of diatomic molecules containing one nitrogen atom and one oxygen atom. It is an intermediate compound in the production of nitric acid from ammonia (CHEMBOOK page 95). Unlike most simple molecules, NO has an odd number of valence electrons (5 from nitrogen and 6 from oxygen), and as a result, it reacts readily with other substances.

Over the last few years medical scientists and chemists have shown that nitric oxide plays an important role in the human body. Apart from water, much of the body is made up of large and immensely complicated organic compounds (proteins, carbohydrates, lipids, enzymes, and so on), so it is always interesting to discover that a simple inorganic compound such as nitric oxide plays an important biological role.

Nitric oxide is one of a series of compounds of nitrogen and oxygen, which are often referred to collectively by the name “oxides of nitrogen” and by the generic formula NO_x. The main oxides of nitrogen are listed below.

N₂O nitrous oxide

NO nitric oxide

N₂O₃ dinitrogen trioxide

NO₂ nitrogen dioxide

N₂O₄ dinitrogen tetroxide

N₂O₅ dinitrogen pentoxide

Air contains about 21 per cent oxygen O₂ and 78 per cent nitrogen N₂ by volume (CHEMBOOK page 103), but we do not normally find oxides of nitrogen in air, except at very low concentrations. This is because these compounds are somewhat unstable; if they are formed they decompose, after a time, into the elements nitrogen and oxygen. Oxides of nitrogen are formed in furnaces and internal combustion engines, and play a role in the chemistry of the atmosphere (CHEMBOOK page 215, Oxtoby page 624).

Several of the oxides of nitrogen are corrosive and poisonous, but two of them have important effects in the body. First, nitrous oxide, N₂O, has long been used as an anaesthetic gas; it is sometimes called “laughing gas” because of its intoxicating effects. Second, nitric oxide, NO, has been shown to cause relaxation of blood vessels, and is therefore a key to treating heart problems and related ailments.

The discovery of the physiological effects of nitric oxide led to the award of the 1998 Nobel prize for Medicine to R.F.Furchgott, L.J.Ignarro, and F.Murad. These three American scientists work in the general area of pharmacology, which is the science of drugs.

Their work showed that nitric oxide acts as a signal transmitter between cells. The most important effect of nitric oxide is to relax the walls of blood vessels, an effect called vasodilation. The result is lower blood pressure and an increase in the flow of blood.

The mechanism by which nitric oxide acts as a “vasodilator” is complicated, and is still under investigation. The physiological effects are the result of the interaction between the NO molecule and the complex organic molecules that form the blood vessels.

There are two interesting areas of medicine in which the physiological effects of nitric oxide play a central role: heart disease and sex.

Take heart disease first. Atherosclerosis is a heart condition in which chest pain, called angina pectoris, is caused by an inadequate supply of blood to the heart. For over a century, doctors have prescribed nitroglycerine pills as a pain reliever for patients suffering from angina. The molecular formula of nitroglycerine is C₃H₅N₃O₉ and the structural formula is:

H₂C–ONO₂

HC–ONO₂

H₂C–ONO₂

Recent research has shown that, in the body, nitroglycerine releases nitric oxide, which in turn dilates the blood vessels and allows more blood to flow to the heart. The chemistry of this process is complicated, and is the subject of current research by Professor Greg Thatcher and others at Queen’s.

Nitroglycerine is also used as an explosive (CHEMBOOK page 214, Oxtoby pages 90 and 765-766). The nineteenth century industrialist Alfred Nobel became immensely wealthy as a result of his development of nitroglycerine into the practical explosive called dynamite. The income from his endowment is used to finance the Nobel prizes, which have been awarded annually since the beginning of the twentieth century.

Alfred Nobel suffered from angina, and was prescribed nitroglycerine to relieve the pain. He wrote: “It sounds like an irony of fate that I have been prescribed nitroglycerine internally. They have named it Trinitrin in order not to upset the pharmacists.”

The 1998 Nobel prize for Medicine was awarded to the three people who discovered how nitric oxide and nitroglycerine work in the body. The interesting historical link is that the money for the prize was derived from the sale of nitroglycerine as an explosive.

Now for sex. Erection of sexual organs occurs by dilation of the appropriate blood vessels, and is triggered by nitric oxide. This is how the anti-impotence drug Viagra works. No wonder the journal Science named nitric oxide in 1992 as Molecule of the Year!