The endogenous nucleoside adenosine can induce various cardiovascular and neurohumoral effects by stimulation of specific adenosine receptors. taken together these effects protect against ischaemia-reperfusion injury of (myocardial)muscles and agsinst the development of atherosclerosis. Genetic variations in genes encoding for adenosine receptors or for enzymes involved in the formation or breakdown of adenosine could potentially modulate these effects. In this study, we aim to determine the functional effects of two frequent genetic polymorphisms in the adenosine receptor and AMPdeaminase (involved in the formation of adenosine) on the vascular effects of adenosine.

Condition	Intervention
Blood Flow in Healthy Volunteers	Drug: Intra-arterial infusion of adenosine  Drug: intra-arterial infusion of caffeine  Drug: intra-arterial infusion of acetylcholine  Drug: intra-arterial infusion of sodium nitroprusside  Procedure: Occlusion of arm-circulation by inflation of upper-arm cuff to 200mmHg for 2, 5 and 13 minutes

Further study details as provided by Radboud University:

Primary Outcomes: A2A: adenosine- and caffeine induced vasomotion (blood flow); AMPD:post-occlusive reactibe hyperemic blood flow
Expected Total Enrollment:  100

The endogenous nucleoside adenosine can induce various cardiovascular and neurohumoral effects by stimulation of specific adenosine receptors. taken together these effects protect against ischaemia-reperfusion injury of (myocardial)muscles and agsinst the development of atherosclerosis. Genetic variations in genes encoding for adenosine receptors or for enzymes involved in the formation or breakdown of adenosine could potentially modulate these effects. In this study, we aim to determine the functional effects of two frequent genetic polymorphisms in the adenosine receptor and AMPdeaminase (involved in the formation of adenosine) on the vascular effects of adenosine.

In 100 healthy young volunteers, we will determine the genotype of the adenosine A2A receptor gene. We expect to find approximately 15 subjects with the 1976T>C polymorphisms. It is known that this polymorphism is associated with an increased neuropsychological sensitivity to caffeine administration.

We will explore whether this polymorphism is associated with a different vasodilating response to the administration of adenosine and caffeine into the brachial artery. Blood flow will be measured with venous occlucion plethysmography.

Secondly, we will also determine the genotype of the AMPD1 gene. We expect to find 15 subjects with the 34C>T mutation, which is a loss-of-function-mutation. Cardiovascular patients with this mutation are known to have a survival benefit. We will explore whether the post-occlusive reactive hyperemia in the forearm is potentiated, because during ischaemia, more adenosine is formed in these subjects.

Ages Eligible for Study:  18 Years   -   40 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• 18-40 year

Exclusion Criteria:

• hypertension
• diabetes
• cardiovascular or pulmonary disease
• asthma

Please refer to this study by ClinicalTrials.gov identifier  NCT00253929

Niels Riksen, MD      +31-24-3613691    N.Riksen@aig.umcn.nl

Netherlands, Gelderland
      Radboud University Nijmegen Medical Centre, Nijmegen,  Gelderland,  6500HB,  Netherlands

Study chairs or principal investigators

Gerard Rongen, MD, PhD,  Principal Investigator,  Radboud University   
Paul Smits, MD, PhD,  Principal Investigator,  Radboud University   

Study ID Numbers:  SNPAdenosine; ZonMw Nr. 920-03-249
Last Updated:  December 8, 2005
Record first received:  November 11, 2005
ClinicalTrials.gov Identifier:  NCT00253929
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
ClinicalTrials.gov processed this record on 2006-01-10