The Effect of Antioxidants on Skin Blood Flow During Local Heating

The integrative vascular laboratory has recently observed that the small blood vessels in the
skin (the cutaneous microvasculature) in obese (BMI>30kg/m2), but otherwise healthy
individuals, require a greater amount of nitric oxide (NO) to achieve the same degree of
dilation when compared to age, gender, and race matched lean (BMI<25kg/m2) individuals (34).
In addition, it is well documented that African Americans have impaired blood vessel function
which likely contributes to the elevated risk for developing a variety of cardiovascular and
metabolic diseases including coronary artery disease, metabolic syndrome, hypertension and
stroke in this population. The cutaneous circulation is recognized as a surrogate vascular
bed for assessment of mechanisms underlying systemic vascular disease (7, 20, 22). This is
particularly important as microvascular dysfunction is emerging as a critical step in the
atherosclerotic process and a variety of conditions including hypertension, exercise
intolerance, and insulin resistance (25). Furthermore, impaired cutaneous microvascular
function mirrors impaired responses in other vascular beds (7, 12, 20, 22). A primary
advantage to utilizing the cutaneous circulation is that it provides an accessible vascular
bed through which processes of endothelial function can be systematically and mechanistically
investigated, with virtually no risk, through thermal stimuli and local intra-dermal drug
infusions. Mechanisms of impaired NO bioavailability have been assessed in various at-risk
and diseased populations including, healthy aging, hypertension, postural tachycardia
syndrome, hypercholesteremia, and chronic kidney disease (8, 16, 19, 24, 36, 37). Using
approaches and techniques similar to those proposed in this application (see below) the
findings have implicated that a number of factors, including elevated oxidative stress,
contribute to the reduced bioavailability and/or action of NO (8, 16, 19, 24, 36, 37)

The recent findings suggest an impairment in the action of NO on the microvascular smooth
muscle of obese young adults (34) as well as in college-aged otherwise healthy African
Americans. Local heating is a common method to test nitric oxide-mediated vasodilation (3, 6,
31). Therefore, the investigators propose to test the following hypotheses:

1. Obesity results in impaired blood flow response to local heating and this will also be
the case for African Americans.

2. Inhibition of superoxide, a common form of oxidative stress, augments the local heating
response in obese individuals as well as in African Americans.

3. Inhibition of sources of superoxide, NADPH-oxidase and/or Xanthine-oxidase, augments
skin blood flow local heating response in obese to that of their lean counterparts. This
will also be the case for African Americans relative to their Caucasian American
counterparts.

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