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  The Viagra™ story
            2. Concept
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Viagra's false start

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.

Targetting research

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.

Interactive graphic explaining anatomy vasodilation Interactive graphic explaining anatomy vasodilation
Interactive graphic explaining anatomy vasodilation Interactive graphic explaining anatomy vasodilation
Interactive graphic explaining anatomy vasodilation
Picture 5. Arteries dilate when nitric oxide switches on the enzyme that makes cGMP.
How does vasodilation work?

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.

Choosing the target

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.

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Question 2
How is vasodilation stimulated normally? Put these statements in the correct order:
How does Viagra™ help maintain vasodilation? Put these statements in the correct order:

You can swap two statements by clicking on one, then on the other.
Move the statements by constantly swapping pairs of statements.
Make sure you don't mix up the first set with the second set.

The enzyme guanylate cyclase makes cGMP.
Nerve cells cause the release of nitric oxide in artery walls.
cGMP relaxes muscles in the artery wall.
The artery opens up or vasodilates.
Nitric oxide switches on an enzyme called guanylate cyclase.
This helps to maintain the vasodilation.
Normally an enzyme called PDE will break down the cGMP.
Viagra keeps levels of cGMP high.
Viagra inhibits the activity of the PDE.