Mechanisms of cutaneous microvascular endothelial dysfunction in young black Americans
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Black Americans have an increased risk for developing a variety of cardiovascular disease (CVD) when compared to white Americans and other populations in the United States. It has also been demonstrated that the underlying impairments in black Americans manifest during early adulthood prior to any overt signs of risk, which leads to higher rates of CVD related morbidity and mortality in black Americans than other populations. Study 1 was designed to investigate the potential mechanisms of cutaneous microvascular dysfunction in young college-age black Americans. This was assessed by measuring the skin blood flow response to local heating while various vasoactive substances were delivered into the cutaneous interstitial space by intradermal microdialysis. We demonstrated that an attenuated nitric oxide (NO) mediated vasodilation due in part to a relative deficit of L-arginine in the endothelial cells is one mechanism by which microvascular dysfunction occurs in young black Americans. Study 2 conducted to investigate the effects of acute cocoa flavanol intake on cutaneous microvascular function in young black Americans. This was assessed by measuring the skin blood flow response to local heating and delivery of vasoactive substances (as described above) before and after consumption of a beverage high in flavanol content. Study 2 demonstrated that acute flavanol intake improved cutaneous microvascular function in response to local heating in young black Americans relative to young white Americans. Study 3 was designed to investigate the effects of acute flavonal intake on endothelium-dependent microvascular dilation in response to exogenous administration of methacholine (MCh) in young black Americans. This was assessed by skin blood flow responses to incremental dose of MCh, which was delivered by intradermal microdialysis, before and after consumption of a beverage high in polyphenol content. Study 3 identified that acute flavanol intake did not alter the dose-response curve of MCh-induced cutaneous vasodilation in either racial groups. Overall, the series of studies in this dissertation may provide evidence that young black Americans have attenuated microvascular function relative to young white Americans, and that a potential mechanism of decreased microvascular function is a decrease in NO bioavailability and/or NO mediated vasodilation, which is related to a deficit of L-arginine in the endothelial cells in young black Americans. Furthermore, our findings may provide evidence that the consumption of cocoa flavanols is an effective therapeutic strategy to prevent and/or delay the development of CVD at least in young black Americans.