G-alpha proteins and their effectors (AC, PLC, rho and ERK) in central cardiovascular regulation in health and disease

高血压是心血管疾病的主要危险因素，如中风，这是巨大的情感和经济社会负担。大脑对控制血压至关重要。大脑中的特定部位在设定血压的静息水平和控制血压以响应诸如躺着或站立等刺激方面至关重要。这些大脑部位的活动在高血压等情况下会发生变化。我们将确定细胞内的特定蛋白质在控制血压中的作用，这些蛋白质在大脑中的细胞间通讯中很重要。大脑中的细胞通过作用于细胞表面受体的化学信使进行交流。这些受体存在三种形式。我们感兴趣的是最丰富的受体形式，大约有860个成员。当这些受体被激活时，它们使用细胞内复杂的蛋白质级联来决定细胞的反应。我们知道，大脑中的这些受体中有一些参与血压的调节，其中一些在高血压等疾病中发生改变。我们可以靶向每一种受体，但对于其中许多受体，我们不知道激活它们的化学物质。幸运的是，860种受体中的每一种主要通过几种专门的蛋白质起作用。最初，我们将靶向这些蛋白质，以确定这些受体在改变血压的静息水平方面的影响，它们在响应影响血压的刺激时的作用以及它们在高血压中的作用。将采用三种方法：改变蛋白质的功能，识别存在的蛋白质类型，识别参与的细胞，在大脑中对心脏和血管的调节很重要。这种了解大脑如何控制血压的新方法无疑将确定新的降血压疗法的目标和高血压基因决定原因的目标。

High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific proteins within cells, which are important in cell to cell communication in the brain, have in the control of blood pressure. Cells in the brain communicate using chemical messengers that act at receptors on the cells surface. Three forms of these receptors exist. We are interested in the most abundant form of receptor that has about 860 members. When activated these receptors use a complex cascade of proteins within the cell to dictate that cell's response. We know that some of these receptors in the brain are involved in the regulation of blood pressure and that some of them are altered in conditions such as hypertension. We could target each of the receptors but for many of them we do not know the chemical than activates them. Fortunately each of 860 receptors act primarily via just a few specialised proteins. Initially we will target these proteins to determine the impact these receptors have in altering the resting levels of blood pressure, their role in response to stimuli that affect blood pressure and the role they play in hypertension. Three approaches will be used: altering function of the proteins, identifying the types of proteins present and identifying the cells involved, in brains sites important in regulation of the heart and blood vessels. This novel approach to understanding how the brain controls blood pressure will undoubtedly identify targets for novel blood pressure lowering therapies and targets for genetically determined causes of hypertension.