Gap Junction Potentiation of Endothelial Function With Rotigaptide
Status:
Completed
Trial end date:
2015-08-03
Target enrollment:
Participant gender:
Summary
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-arterial rotigaptide infusion the investigators want to assess any functional
preservation.
Phase:
N/A
Details
Lead Sponsor:
University of Edinburgh
Collaborators:
Chief Scientist Office of the Scottish Government NHS Lothian