Renal medullary blood flow: regulation by paracrine, endocrine and neural factors

高血压是一种困扰我们社区10%以上的疾病，是中风和心脏病的主要危险因素。在正常情况下，肾脏在控制血压方面起着关键作用，也可能在高血压的发生和维持中起着关键作用。这种影响是通过盐和水的排泄以及影响血压的物质（激素）释放到循环中来实现的。我们和其他人最近进行的实验表明，肾脏的内部（髓质）在这些功能中至关重要，这些功能似乎受到肾脏髓质中血流水平的调节。我们最近的实验还表明，激素和神经对肾脏不同区域的血流有不同的影响，表明这些因素可以根据其对髓质血流的影响而不同地影响血压。重要的是，这些激素和神经不会单独起作用，而是协同作用，并与所谓的“第二信使”系统相关联，该系统局部作用以直接影响血管中肌肉的收缩，从而影响血管大小。本申请中描述的实验旨在确定循环和局部作用激素以及肾脏中的神经如何相互作用以控制肾脏不同区域中的血流。这将帮助我们了解血液流向肾脏髓质是如何正常调节的，这样我们就可以开始了解这些系统的功能障碍如何导致高血压的发生。

High blood pressure is a condition afflicting more than 10% of our community, and is the leading risk factor for stroke and heart disease. The kidneys play a critical role in control of blood pressure under normal conditions, and probably also in the initiation and maintenance of high blood pressure. This influence is exerted both through the excretion of salt and water, and by the release of substances into the circulation that affect blood pressure (hormones). Recent experiments performed by us and others have indicated that the inner part of the kidney (the medulla) is critical in these functions, which appear to be regulated by the level of blood flow in the medulla of the kidney. Our recent experiments also show that hormones and nerves have diverse effects on blood flow in the different regions of the kidney, showing that these factors can differentially affect blood pressure depending on their effects on medullary blood flow. Importantly, these hormones and nerves do not act in isolation, but act in concert, and in association with so called 'second messenger' systems that act locally to directly affect the contraction of muscle in blood vessels, and so blood vessel size. The experiments described in this application are aimed at determining how circulating and locally acting hormones, and the nerves in the kidney, interact together to control blood flow in the different regions of the kidney. This will help us understand how blood flow to the medulla of the kidney is regulated normally, so that we can begin to understand how malfunction of these systems can contribute to the development of high blood pressure.