The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction

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.

Inclusion Criteria:

- Individuals (ages 18-35, both genders) will be recruited from the greater Arlington
area to participate in the study.

- Must self-report both parents as either African American or Caucasian American.

Exclusion Criteria:

- Individuals who have donated more than 550 ml of blood within the past 8 weeks will
not have blood drawn from them in this protocol. However, if they remain interested in
the study, and otherwise meet the inclusion criteria, than we may still opt to proceed
with data collection.

- Individuals with cardiovascular, neurological, and/or metabolic illnesses will be
excluded from participating as well as individuals with a history of various diseases
of the microvasculature including Reynaud's disease, cold-induced urticaria,
cryoglobulinemia, etc.

- Subjects currently taking any prescription medications and individuals with a body
mass index about 30 kg/m2) will be excluded.

- Pregnant subjects and children (i.e. younger than 18) will not be recruited for the
study. Eligible females will be scheduled for days 2-7 of their menstrual cycle to
account for hormonal effects on blood flow. A regular menstrual cycle is required to
identify and schedule the study for the low hormone period, therefore females who lack
a regular cycle will be excluded from the study. Females currently taking birth
control are eligible, as long as they can be scheduled during a low-hormone "placebo"
week. If their hormone do not contain a placebo week than these individuals will not
be eligible for data collection. Females who are breast-feeding will also be eligible
as there are no systemic or lasting effects of the proposed vasoactive agents.

- Given that smoking can affect the peripheral vasculature, current smokers and
individuals who regularly smoked (>1 pack per two weeks) within the prior 2 years will
be excluded