Apelins are substances which occur naturally in the body, and have an important role in heart disease. They have been shown to make blood vessels dilate, and improve the way the heart works.

The investigators have devised 2 sets of experiments to investigate how the apelins affect blood vessels.

In the first group of experiments,the investigators will give healthy volunteers up to 3 different apelin substances, and use special research techniques to see how they affect the way that blood vessels work in the forearm.

In the second group of experiments, the apelins will be given along with another form of apelin which blocks the effects of apelin in laboratory experiments. The investigators want to see if it blocks the effects of apelin in healthy humans.

The investigators intend to test the hypothesis that:

Apelin agonists are vasodilators in human resistance vessels, this effect will be blocked by an apelin receptor antagonist.

This study will help us to understand more about how apelins work, and to suggest how they might be used to treat heart disease.

Inclusion Criteria:

• Between 18 and 70 years
• Non-regular smoking (<5 cigarettes per week)
• If female, postmenopausal or on days 2-9 of menstrual cycle

Exclusion Criteria:

• Hypertension (sustained BP >160/100mmHg)
• Ischaemic Heart Disease
• Renal, respiratory or neurological disease
• Diabetes mellitus
• BMI >30, BMI <18
• Pregnant
• Smoker
• Use of vasoactive medication or NSAIDS/aspirin within 48 hours of study.
• Current involvement in other research studies