Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?
Status:
Completed
Trial end date:
2009-09-01
Target enrollment:
Participant gender:
Summary
Rationale:
Statins form a class of drugs that is widely prescribed for hypercholesterolaemia,
specifically to reduce the risk on atherosclerosis by lowering LDL-cholesterol. Next to the
effect for which the drug was originally developed, it became obvious that statins have
several other beneficial effects. Such pleiotropic effects include the activation of
ecto-5'-nucleotidase which can increase endogenous adenosine production (by dephosphorylation
adenosine monophosphate into adenosine) and subsequently cause vasodilation. A recent study
of Meijer et al (not yet published) showed that rosuvastatin significantly augments
vasodilation after a brief period of ischemia (post occlusive reactive hyperaemia). However,
it is not yet verified whether this increase in post occlusive reactive hyperaemia is truly
caused by a rise of extracellular adenosine and subsequent adenosine receptor stimulation. In
this study, the mechanism by which rosuvastatin augments post occlusive reactive hyperaemia
will be investigated by blocking adenosine receptors with caffeine, a competitive A1 and A2
adenosine receptor antagonist. Caffeine is a substance that can be safely used in normal
concentrations to block the adenosine receptor.
Hypothesis:
The augmenting effect of rosuvastatin on PORH is caused by an increase of extracellular
adenosine formation and this effect can be diminished by blocking the adenosine receptor
using caffeine.
Objective:
To study the influence of caffeine on post occlusive reactive hyperaemia before and after 7
days treatment with rosuvastatin.
Study design:
Open label cross-over design Study population: Healthy volunteers, 18-50 years of age
Intervention:
Eight volunteers will receive a 7 day treatment with rosuvastatin 20 mg daily before and
after rosuvastatin treatment caffeine will be administrated intra-arterially.
Main study parameters/endpoints:
Forearm blood flow (FBF) will be measured as an indicator for post occlusive reactive
hyperaemia (PORH).