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Effect of Polymorphisms in the Adenosine a2a Receptor Gene and AMPD2 Gene on Adenosine-Induced Vasodilation and Reactive Hyperemia

2014-08-27 03:47:38 | BioPortfolio

Summary

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.

Description

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.

Study Design

Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Conditions

Blood Flow in Healthy Volunteers

Intervention

Intra-arterial infusion of adenosine, intra-arterial infusion of caffeine, intra-arterial infusion of acetylcholine, intra-arterial infusion of sodium nitroprusside, Occlusion of arm-circulation by inflation of upper-arm cuff to 200mmHg for 2, 5 and 13 mi

Location

Radboud University Nijmegen Medical Centre
Nijmegen
Gelderland
Netherlands
6500HB

Status

Completed

Source

Radboud University

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:47:38-0400

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