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

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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.