Local Antioxidant Therapy Vasoconstriction Effects in Different Races

Summary

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. Our laboratory has recently observed (UTA IRB 2016-0268) that 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 various antioxidants abolishes this skin blood flow difference. These antioxidant drugs inhibit possible sources of ROS, which, as mentioned, maybe mediating the heightened vasoconstrictor response in BL. However, this has not been investigated in this population and thus remains unknown. Therefore, the purpose of this study proposal is to test the following hypotheses: 1) BL will have a greater reduction in cutaneous blood flow in response to local administration of Norepinephrine (alpha1-adrenergic and alpha 2-adrenergic receptor agonist) relative to WH. 2) This greater reduction in the BL population will be related to elevated oxidative stress and subsequent reduction in bioavailability of the potent vasodilator Nitric oxide.

Conditions

• Cardiovascular Diseases
• Cardiovascular Risk Factor
• Vasoconstriction

Interventions

DRUG

Control (Norepinephrine)

This intervention is aimed at assessing the vascular responsiveness to norepinephrine, an alpha 1-agonist, in white and black men and women across a series of ascending dose concentrations.

DRUG

Norepinephrine + Ascorbic Acid

This intervention is meant to globally assess the impact of oxidative stress on vasoconstrictor responses by scavenging numerous oxidative molecules.

DRUG

Norepinephrine + L-NAME

This intervention is meant to assess the impact of endothelium-derived nitric oxide on vasoconstrictor responses by inhibiting production of this source of nitric oxide.

DRUG

Norepinephrine + L-NAME + Ascorbic Acid

This intervention is meant to assess the combined impact of scavenging oxidative stress and inhibiting endothelium-derived nitric oxide on vasoconstrictor responses.

Sponsors & Collaborators

• The University of Texas at Arlington

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-10-15

Primary Completion

2024-05-15

Completion

2024-06-08

FDA Drug

Yes

Countries

• United States

Study Locations