Local Antioxidant Therapy Vasoconstriction Effects in Different Races

Study 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.

Primary Outcome

Establish heightened vasoconstriction to norepinephrine stimulation in black men and women with a focus on black women. Following the local infusion of norepinephrine, the changes in blood flux will be quantified using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of baseline flux.

Interventions

• DRUG Control (Norepinephrine)
• DRUG Norepinephrine + Ascorbic Acid
• DRUG Norepinephrine + L-NAME
• DRUG Norepinephrine + L-NAME + Ascorbic Acid