Gap Junction Potentiation of Endothelial Function With Rotigaptide

Hypothesis - Rotigaptide will improve endothelial function in the context of endothelial dysfunction. The lining of blood vessels (endothelium) can react to hormones in the blood stream causing the blood vessel muscle to relax (vasodilatation) and allow more blood to flow. The nitric oxide and prostacyclin pathways are well documented in this process. However, evidence points to the existence of a third powerful relaxant called endothelium derived hyperpolarising factor (EDHF) but its identity and mechanism of action have proved elusive. As well as causing blood vessels to relax and more blood to flow, EDHF may be involved in the endothelium signaling, triggering release of a specialised clot dissolving factor called tissue plasminogen activator (t PA). t PA is important to ensure small clots, which are constantly being formed in the circulation, are rapidly dissolved and do not grow large enough to cause heart attacks and strokes. Evidence points towards the requirement for 'gap junctions' in the mediation of EDHF responses. Gap junctions are specialised pores which allow small molecules and charge to pass between cells. They are found between endothelial cells and the underlying muscle of the blood vessel. A drug called Rotigaptide has been developed to cause gap junctions to open. It has been safely administered in healthy volunteers and is now in a Phase II drug trial. By opening gap junctions the investigators hypothesise that it could increase EDHF mediated activity and vasodilatation. It represents a useful tool with which to examine the role of gap junctions in EDHF activity in vivo. Previously the investigators have demonstrated that rotigaptide does not contribute to endothelial function in healthy volunteers. The investigators now wish to examine the effect of rotigaptide in conditions of endothelial dysfunction. By limiting the blood flow to the arm for 20mins the ability of the blood vessel to vasodilate is impaired. By administering an intra-arteria