Sympathetic nervous system contribution to hypertension : CNS pathways, neurotransmitters and neuroeffector mechanisms

高血压（hypertension）是西方社会的一个主要公共卫生问题，大约有20%的成年人受到影响。如果不及时治疗，可能会对器官造成严重损害，心脏性猝死或中风的风险也会大大增加。虽然许多因素导致高血压的发展，如生活方式、基因、饮食、体重和运动水平，但早期阶段的一个共同特征是肾脏和心脏的神经系统过度活跃，这很可能是由于大脑信号的改变。我们需要了解为什么会发生这种情况。一种可能是肾素（一种从肾脏释放的化学物质）控制体液，它也在大脑中作用，增加肾脏和心脏的神经活动，从而导致高血压。它通过产生另一种叫做血管紧张素的激素间接做到这一点。我们的研究表明，在肾脏释放过多的肾素的情况下，如果肾脏的血液供应减少，可能会发生这种情况，神经系统影响血压的方式就会发生变化。神经系统被激活，增加肾素从肾脏的释放。这样做的结果是使血压进一步升高，从而形成恶性循环。目前还不清楚这种变化发生的原因和方式。该项目的主要目的是确定肾脏激素向中枢神经系统发出信号的机制，从而将神经活动的性质改变回肾脏。我们想知道大脑的哪些部分参与其中，神经活动的性质如何变化，以及肾脏的神经控制如何变化（即肾脏如何改变其对神经活动的反应）。因为类似的过程可能发生在几乎所有形式的高血压中，我们的研究结果将大大提高我们对这种危险状况如何发展的理解。

High blood pressure (hypertension) is a major public health problem in Western society with approximately 20% of adults affected. If left untreated, serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyle, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely due to altered signals from the brain. We need to understand why this occurs. One possibility is that renin (a chemical released from the kidney) that is known to control body fluid, also acts in the brain to increase nerve activity to the kidney and heart and in this way contributes to high blood pressure. It does this indirectly by producing another hormone called angiotensin. Our research has shown that in conditions where the kidney releases excess of the hormone renin, which may occur if the blood supply to the kidney is reduced, a change occurs in the way in which the nervous system affects blood pressure. The nervous system is activated to increase the release of renin from the kidney. The effect of this is to make blood pressure increase further in what can become a vicious circle. At present it is not understood why and how this change occurrs. The major thrust of this project is to determine the mechanims by which the renal hormones signal the central nervous system to change the nature of the nervous activity back to the kidney. We want to know what parts of the brain are involved, how the nature of the activity in the nerves changes and also how the nervous control of the kidney changes (i.e. how the kidney changes its responsivness to the nerve activity). Because similar processes probably occur in nearly all forms of high blood pressure, our results will greatly improve our understanding of how this dangerous condition develops.