Pyridoxine, P2 Receptor Antagonism, and ATP-mediated Vasodilation in Young Adults
Condition: Receptor Blockade
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Previous research has identified adenosine triphosphate (ATP) as an important vasodilator
      that is released from red blood cells during exercise and exposure to hypoxic environments in
      adult humans. Further, older adults appear to have lower blood flow during both of these
      stressors and also have lower amounts of ATP released from their red blood cells. However,
      the contribution of ATP to vasodilation in response to exercise and hypoxia is currently
      unknown due to the lack of an effective ATP receptor antagonist. We aim to determine whether
      Vitamin B6 or its metabolite, Pyridoxal-5-Phosphate (PLP) is an effective ATP receptor
      antagonist.
    

Detailed description: 
      Adenosine triphosphate (ATP) is an established vasodilator that is released from red blood
      cells during a variety of stimuli including exercise and exposure to hypoxic environments.
      Many studies have shown that infusion of ATP can lead to vasodilation similar to that which
      is achieved during exercise, and that plasma ATP concentrations increase in a graded fashion
      during graded exercise. Further, older adults have lower levels of blood flow during exercise
      and hypoxia compared to their younger counterparts, and the reduced blood flow is coupled
      with impaired release of ATP from red blood cells during these stimuli. Thus, ATP is believed
      to be an important vasodilator. However, the role of ATP in the regulation of blood flow is
      not fully understood due to the lack of an effective ATP receptor (P2Y2) antagonist.
      Development of an effective P2Y2 antagonist will allow researchers to determine the role of
      ATP in vasodilation to stimuli such as exercise by comparing blood flow during exercise with
      and without the blocker. Preliminary data from our laboratory suggests that Vitamin B6
      (pyridoxine hydrochloride) or its metabolite Pyridoxal-5-Phosphate (PLP) may be an effective
      blocker of ATP-mediated vasodilation. As a result, the purpose of this study is to determine
      whether Vitamin B6 or PLP can inhibit vasodilation in response to intra-arterial infusions of
      ATP. This study also aims to determine the specificity of Vitamin B6 or PLP by measuring its
      effect on vasodilation in response to infusion of several other vasodilators.

      Participants will be asked to complete one screening visit and one study visit. Once study
      eligibility has been determined, participants will report to the Human Performance Clinical
      Research Laboratory at Colorado State University following an overnight fast. A physician
      will then place a catheter in the brachial artery of the non-dominant arm, and participants
      will be randomized into one of three study arms to determine which drugs will be infused into
      the artery. Each arm includes ATP and two other vasodilators. The study will begin by
      measuring vasodilation in response to four standard doses of each vasodilator. Vasodilation
      in response to the vasodilators will then be assessed again following infusion of Vitamin B6
      or PLP. Reduced vasodilation to any of the drugs during the second trial will suggest that
      Vitamin B6 or PLP is an antagonist to the channel through which the drug signals. Each study
      visit will last approximately 4-5 hours.
    

Intervention name(s): Adenosine Triphosphate; Acetylcholine; Sodium Nitroprusside; Adenosine Diphosphate; Adenosine Monophosphate; Uridine Triphosphate; Adenosine; Vitamin B 6; Pyridoxal 5'-Phosphate
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): See arm/group descriptions; See arm/group descriptions; See arm/group descriptions; See arm/group descriptions; See arm/group descriptions; See arm/group descriptions; See arm/group descriptions; See arm/group descriptions; See arm/group descriptions
Other intervention name(s): ATP; Ach; SNP; ADP; AMP; UTP; Adenocard; Pyridoxine; Pyridoxine Hydrochloride; PLP; P5P; pyridoxal phosphate monohydrate; MC-1
Intervention MeSH terms: Pyridoxine; Pyridoxal; Vitamin B 6; Pyridoxal Phosphate; Adenosine; Nitroprusside; Acetylcholine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be assigned to one of three arms of the study. The arms of the study are based on the vasodilators being tested in order to determine the effect of pyridoxine or PLP on vasodilation in response to intra-arterial administration of the vasodilators.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Adenosine Triphosphate; Pyridoxine; Cardiovascular; PLP; P5P