Cardiovascular Diseases Clinical Trial
Official title:
The Effect of Antioxidants on Skin Blood Flow During Local Heating
The goal of this study is to examine possible mechanisms of impaired vasodilaton in obese and 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.
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.
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