Effect of Polymorphisms in the Adenosine a2a Receptor Gene and AMPD2 Gene on Adenosine-Induced Vasodilation and Reactive Hyperemia
Condition: Blood Flow in Healthy Volunteers
MeSH terms: Hyperemia
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): 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 minutes
Intervention type(s): Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Adenosine; Nitroprusside; Acetylcholine; Caffeine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: adenosine; polymorphisms; blood flow; adenosine A2a receptor; AMP deaminase