Central regulation of blood pressure : role of angiotensin and nitric oxide

高血压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。一个主要的问题是理解为什么会发生这种情况。一种可能是血管紧张素（一种从肾脏释放的激素，已知可以控制体液）也在大脑中起作用，增加肾脏和心脏的神经活动，从而导致高血压。我们的研究表明，正常情况下，脑血管紧张素的活性相对较小，但在压力或高盐等特定情况下会被激活。这可能是通过消耗抗氧化剂和在大脑中产生氧化应激。随着年龄的增长，压力，缺乏锻炼和其他各种环境的影响，我们的身体不太能够应对氧化应激，这是正常细胞功能的结果。这个项目的主要目的是确定大脑中血管紧张素对高血压的长期贡献是否是由大脑中高水平的氧化应激引起的。如果血管紧张素在大脑中被阻断，我们将观察实验动物是否仍会患上高血压，并观察改变大脑中的氧化应激水平是否会影响这一作用。我们将能够更好地理解大脑中这些分子之间的相互作用，这为开发新的高度特异性药物开辟了道路，这些药物可以防止心脏和肾脏的高水平神经活动，从而防止高血压的发展。

High blood pressure 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 lifestyles, 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. A major question has been to understand why this occurs. One possibility is angiotensin (a hormone 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 contribute to high blood pressure. Our research has shown that normally brain angiotensin has relatively little activity but can be switched on by specific situations such as stress or a high salt. This may be by depleting anti-oxidants and producing an oxidative stress in the brain. With aging, stress, lack of exercise and other various environmental influences our body is less able to cope with oxidative stress which is the result of the normal cells function. The major thrust of this project is to determine whether the long term contribution of angiotensin in the brain to high blood pressure is caused by a high level of oxidative stress in the brain. We will see whether experimental animals still develop high blood pressure if angiotensin is blocked in the brain and see whether changing the oxidative stress levels in the brain affects this role. We will be able to better understand the interplay between these molecules in the brain which opens the way for the development of new highly specific drugs that can prevent the high level of nerve activity to the heart and kidney and hence the development of high blood pressure.