Viagra™ started life as a medicine intended to treat angina pectoris.

Alfred Nobel - an explosives manufacturer - suffered from angina. In 1890 he was prescribed nitroglycerine (called trinitrin) to relieve the pain of angina attacks. It is still used today.

Over 100 years later, the work of Robert Furchgott, Louis Ignarro and Ferid Murad showed that nitric oxide (NO) was an important signalling molecule in the cardiovascular system. It is released from nerve endings and cells lining the walls of blood vessels. The effect is to make the blood vessel relax, or dilate. It is also involved in the prevention of blood clots. In 1998, they received the Nobel Prize for Physiology. The Nobel prizes were set up by the same Alfred Nobel who had been treated with nitroglycerine.

Building on this knowledge, research by other groups is being undertaken to develop new medicines which moderate the actions of nitric oxide for the treament of cardiovascular and other disorders.

Viagra™ was developed as a treatment for angina. Its effects as a vasodilator would have surprising results.

Developing new medicines may seem like an impossible task. How could a new medicine be found to treat angina?

Researchers started by understanding the process of vasodilation - i.e. what makes the arteries dilate.

Nitric oxide is released from nerve endings. It switches on the enzyme (guanylate cyclase) which makes a molecule known as cGMP (full name, cyclic Guanosine Monophosphate). This cGMP triggers smooth muscle in the artery wall to relax and so the blood vessel dilates .

However, the cGMP does not remain active for very long. It is mainly broken down by another enzyme called PDE (Phosphodiesterase). This seems odd but it is in fact essential. It prevents the artery from staying permanently dilated and allows it to be opened and closed as necessary.

The researchers realised that a new medicine, designed to inhibit the PDE enzyme, could be used to increase the natural vasodilation of the coronary arteries and treat angina.

Viagra™ targets PDE and reduces its activity quite dramatically. There are eleven types of PDE which are found in different parts of the body. Viagra™ was found to inhibit the form of the enzyme, called PDE5, which is found in the walls of arteries that feed blood into the penis.

The effect on the coronary arteries was not enough to make it a useful angina treatment but Viagra™ did enhance vasodilation in other areas.