Identification of heterogeneity in vasodilator function in human and rat resistance vessels: potential drug targets?

血管缩小（收缩）和增大（扩张）之间的平衡决定了血管的正常功能。在身体的不同部位，血管控制这种平衡的方式有很多不同。这种差异在高血压和糖尿病等血管疾病中发生了改变，这些疾病在肥胖中很普遍，因此收缩通常大于扩张。然而，这些差异是什么以及它们是如何发生的还没有得到很好的理解。虽然目前治疗血管疾病的药物要么减少血管收缩，要么增加血管扩张，但它们不是针对单个动脉的；这种情况将使我们能够以一种非常特殊的方式控制血管疾病。最近，我们描述了个体血管控制方式之间的差异。这些变化与不同血管扩张方式的差异有关。目的：进一步了解正常血管功能和心血管疾病中血管发生的变化，重点关注正常状态和肥胖相关疾病（如高血压和糖尿病）中血管扩张的方式。-最终目标是确定动脉功能的具体方式，以便确定动脉特异性药物靶点，以非常具体的方式治疗心血管疾病的疾病相关变化。本项目将有助于了解健康和疾病中的血管功能。预期的最终结果是确定身体不同部位不同动脉功能的机制，这样就可以针对特定的个体血管功能来治疗血管疾病。此外，本工作还将验证饮食性肥胖动物模型在人类肥胖和相关心血管疾病的特征和原因方面的相关性。

The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.