Cardiovascular Diseases Clinical Trial
Official title:
The Effect of Antioxidants on Skin Blood Flow-BH4
The goal of this study is to examine possible mechanisms of heightened vasoconstriction in 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
African Americans (AA) not only have a higher prevalence of hypertension but the severity of
the cardiovascular complications related to this condition are greater in this population
relative to other populations. While the underlying causes of this elevated risk are
multifactorial, vascular dysfunction (i.e. impaired vasodilation and/or augmented
vasoconstriction) is believed to be a key contributing factor. The investigators have
recently observed (UTA IRB 2016-0268) that the small blood vessels in the skin (the cutaneous
microvasculature) in AA, but otherwise healthy individuals, have an impaired blood flow
response in the cutaneous circulation to local heating when compared to age, body mass index
(BMI), and gender, matched Caucasians (CA). This blunted response is abolished in AA when the
sites are pre-treated with either Allopurinol or Apocynin which block the production of
xanthine oxidase and NADPH oxidase, respectively. In addition, Tetrahydrobiopterin (BH4) is
critically involved in vascular function. BH4 is a cofactor involved in the conversion of
L-Arginine into the potent vasodilator nitric oxide (NO) by the enzyme endothelial nitric
oxide synthase (eNOS). Reduced bioavailable BH4 leads to elevated oxidative stress and thus
impaired vascular function.
In addition to local heating another commonly utilized research approach to assess
microcirculatory vascular function is via local infusion of the potent vasodilator
methacholine (Mch). Mch is an acetylcholine analog that causes endothelial dependent
vasodilation primarily through stimulation of NO production. Much like the local heating data
mentioned above, our laboratory (data collected while at UT Austin) has demonstrated a
blunted response to Mch in AA relative to CA. However, the role of xanthine oxidase, NADPH
oxidase, and BH4 in this blunted response remains unknown.
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