The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction
Condition: Cardiovascular Diseases; Cardiovascular Risk Factor; Vasoconstriction
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this study is to examine possible mechanisms of heightened vasoconstriction in
      Black/African American men and women as possible links to the elevated prevalence of
      cardiovascular dysfunction and disease. The main targets in this study are sources of
      oxidative stress.
    

Detailed description: 
      Cardiovascular disease (CVD) afflicts nearly one-third of the adult population with all races
      and ethnicities represented in CVD prevalence. Unfortunately, a disparity exists such that
      the black population (BL) is disproportionately affected compared to other groups, including
      the white population (WH). While the underlying cause of this disparity is multifactorial,
      vascular dysfunction (i.e., impaired vasodilation and/or augmented vasoconstriction) is a key
      contributor. As has been previously observed, BL exhibit a heightened vasoconstrictor
      response to both pharmacological (e.g., alpha-adrenergic receptor agonists) and environmental
      (e.g., cold pressor test) stimuli compared to their WH counterparts. Additionally, reactive
      oxygen species (ROS) and the subsequent reduction in nitric oxide (NO) bioavailability may
      partially mediate this response.

      Interestingly, the small blood vessels in the skin (cutaneous microvasculature) in BL, but
      otherwise healthy individuals, produce an impaired blood flow response to local heating when
      compared to age-, body mass index (BMI)-, and gender-matched WH. However, pre-treatment of
      the cutaneous microvasculature with either allopurinol or apocynin (xanthine oxidase
      inhibitor and NADPH oxidase inhibitor, respectively) abolishes this skin blood flow
      difference. These drugs inhibit possible sources of ROS, which, as mentioned, may be
      mediating the heightened vasoconstrictor response in BL. Accordingly, apocynin administration
      in previous research using an animal model ameliorates alpha-adrenergic receptor-mediated
      vasoconstriction, possibly due to a reduction in ROS. The role of xanthine/NADPH oxidase and
      the production of ROS on alpha-adrenergic receptor-mediated vasoconstriction in humans
      remains unknown.
    

Intervention name(s): Control (Phenylephrine); Phenylephrine + Apocynin; Phenylephrine + Allopurinol; Phenylephrine + Tempol
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): This intervention is aimed at assessing the vascular responsiveness to phenylephrine, an alpha 1-agonist, in white and black men and women across a series of ascending dose concentrations.; This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme NADPH oxidase.; This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme xanthine oxidase.; This intervention is meant to assess the impact of superoxide on vasoconstrictor responses by scavenging available superoxide.
Intervention MeSH terms: Allopurinol; Phenylephrine; Oxymetazoline; Tempol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Each subject has one control site and three experimental sites concurrently tested within the same study using intradermal microdialysis on the dorsal forearm.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Racial Differences; Oxidative Stress