Microvascular and sensory nerve function in non-Hispanic Blacks and Whites

项目总结/摘要 该应用程序的广泛长期目标是改善健康结果并减少健康风险。 美国非西班牙裔黑人（NHB）人口的差异。慢性病的发病率，如 高血压（HT）和心血管疾病，在NHB中高于非西班牙裔白人（NHW）。 慢性疾病的后果之一是内皮依赖性血管舒张减少， 假设这部分导致了NHB中慢性病的发病率增加。几项研究 提示与对照组相比，在健康和HT NHB的导管（大）动脉中NO依赖性血管舒张减少， NHW。目前还不太清楚的是高血压前期（PreHT）如何影响微血管内皮细胞- 依赖性血管舒张在许多器官中，微血管和外周血管之间存在相互作用。 神经，如感觉神经。在患者组和NHB中的研究，很少（如果有的话）调查 微血管系统和感觉神经之间的相互作用，因此尚不清楚感觉神经功能是否 与NHW相比，PreHT或NHB降低。人类皮肤提供了一个独特的机会， 微血管和感觉神经之间的相互作用，使用微创技术。加热 已知小面积的皮肤会增加皮肤血流量，并且这种增加是由内皮细胞- 依赖机制和感觉神经介导机制。皮肤循环也是一个容易 可接近的微血管床和皮肤功能障碍与较难接近的区域相关，例如 肾脏和心脏两种分子，一氧化氮（NO）和内皮素-1（ET-1），都是重要的调节剂 但目前尚不清楚这两种分子如何促进微血管感觉神经 NT或PreHT NHB与NHW的相互作用。因此，我们提出两个具体目标：1）确定 NO对NT和PreHT NHB和NHW中皮肤微血管舒张的贡献，以及2）确定 ET-1在NT和PreHT NHB和NHW皮肤微血管舒张中的作用。我们 预计拟议研究的数据将提高我们治疗，更重要的是预防慢性病的能力 疾病在NHB反过来，这将有助于减少NHB人口的健康差距。

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.