NCT03680404

The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: The University of Texas at Arlington · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

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.

Conditions

• Cardiovascular Diseases
• Cardiovascular Risk Factor
• Vasoconstriction

Interventions

Type	Name	Description
DRUG	Control (Phenylephrine)	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.
DRUG	Phenylephrine + Apocynin	This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme NADPH oxidase.
DRUG	Phenylephrine + Allopurinol	This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme xanthine oxidase.
DRUG	Phenylephrine + Tempol	This intervention is meant to assess the impact of superoxide on vasoconstrictor responses by scavenging available superoxide.

Timeline

• Start date: 2018-10-01
• Primary completion: 2020-02-01
• Completion: 2020-02-01
• First posted: 2018-09-21
• Last updated: 2020-11-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study