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

高血压是中风等心血管疾病的主要危险因素，这些疾病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静息血压水平和控制血压以应对诸如躺着或站立等刺激时起着至关重要的作用。这些大脑部位的活动在高血压等情况下会发生改变。我们将确定细胞内的特定蛋白质在控制血压方面的作用，这些蛋白质在大脑细胞间的通讯中很重要。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。这些受体有三种形式。我们感兴趣的是最丰富的受体形式，它有大约860个成员。当被激活时，这些受体利用细胞内复杂的蛋白质级联来指示细胞的反应。我们知道大脑中的一些受体参与了血压的调节，其中一些受体在高血压等疾病中发生了改变。我们可以瞄准每一个受体，但对于其中的许多受体，我们不知道是什么化学物质激活了它们。幸运的是，860个受体中的每一个主要通过一些特殊的蛋白质起作用。首先，我们将以这些蛋白质为目标，确定这些受体在改变静息血压水平方面的影响，它们在对影响血压的刺激的反应中所起的作用，以及它们在高血压中的作用。将使用三种方法：改变蛋白质的功能，识别存在的蛋白质类型和识别涉及的细胞，在大脑中对心脏和血管的调节很重要。这种理解大脑如何控制血压的新方法无疑将为新的降压疗法和基因决定的高血压病因确定目标。

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.