Cerebral and peripheral microvascular function in individuals with elevated cardiovascular disease risk
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The series of studies in this dissertation determined: 1) the effectiveness of a clinically applicable dietary supplement on cerebral vascular function in African Americans (AA), 2) cerebral vascular function in obese individuals, and 3) the underlying mechanism of cutaneous microvascular dysfunction in AA. Study #1 identified that acute flavanol consumption improves cerebral vasodilatory capacity in response to rebreathing-induced hypercapnia in AA. Our laboratory previously found that hypercapnia-induced cerebral vasodilation is reduced in AA when compared with Caucasian Americans (CA). Findings in study #1 may provide an effective interventional strategy to mitigate the high incidence of cerebral vascular diseases, which is commonly found in AA. Study #2 assessed the cerebral vasodilatory capacity in obese individuals. Cerebral vasodilation during hypercapnia, as indexed by the total range of change and the maximal increase in cerebral vascular conductance, was decreased in obese individuals relative to lean counterparts. This attenuated response in obese individuals may explain why they are at higher risk for cerebral vascular diseases including Alzheimer’s disease and stroke. In study #3, mechanisms underlying impaired cutaneous microvascular thermal reactivity in AA were explored using an intradermal microdialysis technique. Our preliminary data previously found that cutaneous vasodilation in response to local heating is decreased in AA. As a follow-up study, we assessed cutaneous vasodilation using pharmacological agents ascorbic acid and tempol, a global antioxidant and superoxide-specific scavenger, respectively. Study #3 determined that reduced cutaneous microvascular thermal reactivity in AA is mainly due to elevated concentration/activity of superoxide. Collectively, the series of studies in the current dissertation provide a potential therapeutic strategy to ameliorate the vascular impairment as well as potential mechanisms for elevated cerebral and peripheral vascular dysfunction in individuals with elevated risk of cardiovascular diseases for future clinical/mechanistic investigations.