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

项目摘要/摘要 这项应用的广泛、长期目标是改善健康结果和减少健康 美国非西班牙裔黑人(NHB)人口的差异。慢性病发病率，例如 与非西班牙裔白人(NHW)相比，NHB中高血压(HT)和心血管疾病的发病率更高。 慢性疾病的后果之一是内皮依赖性血管扩张功能减弱，而且 假设这是NHB慢性病发病率增加的部分原因。几项研究 提示健康和高血压性非酒精性血友病患者导管(大)动脉的NO依赖性血管扩张功能较健康人和高血压性心脏病患者减少 啊哈。目前不太为人所知的是高血压前期(PreHT)如何影响微血管内皮细胞- 依赖性血管扩张。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中进行的研究，很少(如果有的话)调查 微血管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减少。人类皮肤为我们提供了一个研究 微创技术在微血管和感觉神经之间的相互作用。供暖 众所周知，小面积皮肤可以增加皮肤血流量，这种增加是由内皮细胞和血管内皮细胞共同调节的。 依赖机制和感觉神经介导的机制。皮肤循环也很容易 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。一氧化氮(NO)和内皮素-1(ET-1)这两个分子都是重要的调节因子 但这两个分子对微血管感觉神经的作用尚不清楚 NT或PreHT NHB与NHW的相互作用。因此，我们提出了两个具体目标：1)确定 NO在NT、PreHT、NHB和NHW患者皮肤微血管扩张中的作用 ET-1在NT、PreHT、NHB和NHW患者皮肤微血管扩张中的作用我们 预计来自拟议研究的数据将提高我们治疗慢性疾病的能力，更重要的是，预防 NHB中的疾病。反过来，这将有助于缩小NHB人群的健康差距。

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.