PROJECT SUMMARY/ABSTRACT The broad, long-term objective of this application is to improve health outcomes and reduce health disparities in the non-Hispanic Black (NHB) population in the United States. Rates of chronic disease, such as hypertension (HT) and cardiovascular disease, are higher in NHB compared to non-Hispanic Whites (NHW). One of the consequences of chronic disease is reduced endothelial-dependent vasodilation and it is hypothesized that this partially contributes to the increased rates of chronic disease in NHB. Several studies suggest NO-dependent vasodilation is reduced in conduit (large) arteries in healthy and HT NHB compared to NHW. What is currently less well-known is how prehypertension (PreHT) affects microvascular endothelial- dependent vasodilation. In many organs, there is an interaction between the microvasculature and peripheral nerves, such as sensory nerves. Studies in patient groups and in NHB, rarely, if ever, investigate the interaction between the microvasculature and sensory nerves so it is unclear if sensory nerve function is reduced in PreHT or in NHB compared to NHW. Human skin presents a unique opportunity to investigate the interaction between the microvasculature and sensory nerves using minimally-invasive techniques. Heating small areas of skin is known to increase skin blood flow and the increase is regulated by both endothelial- dependent mechanisms and sensory nerve-mediated mechanisms. The cutaneous circulation is also an easily accessible microvascular bed and dysfunction in the skin is correlated with less accessible regions, such as the kidney and heart. Two molecules, nitric oxide (NO) and endothelin-1 (ET-1), are both important regulators of vascular function but it is unknown how these two molecules contribute to microvascular-sensory nerve interactions in NT or PreHT NHB vs. NHW. We therefore propose two specific aims: 1) determine the contribution of NO to cutaneous microvascular vasodilation in NT and PreHT NHB and NHW, and 2) determine the contribution of ET-1 to cutaneous microvascular vasodilation in NT and PreHT NHB and NHW. We anticipate the data from the proposed studies will improve our ability to treat, and, importantly, prevent, chronic disease in NHB. This, in turn, will help reduce health disparities in the NHB population.