Brain angiotensin: generation, localisation and physiological function

肾素血管紧张素系统是人体内调节心血管系统和体内盐水平衡的主要同源系统之一。通过降低血液中血管紧张素II的水平或阻断其作用的受体来抑制这一系统功能的药物是治疗高血压和心力衰竭的前沿药物。有人提出，由于血脑屏障的存在，血流中不受血管紧张素II影响的独立的脑肾素血管紧张素系统存在。在小鼠品系中，编码这一系统的两个组成部分--血管紧张素转换酶(负责产生血管紧张素II的酶)和血管紧张素原(产生血管紧张素II的蛋白质)的基因为阐明大脑中的这一系统提供了极好的工具。通过对这些小鼠的研究，我们将能够确定大脑中是否需要血管紧张素转换酶来预防血管紧张素II，我们将能够确定大脑中存在真正的血管紧张素肽的位置。我们还将确定血管紧张素II是否在大脑中的神经元之间传递信息，这些神经元在控制心血管系统和体液平衡方面发挥作用。

The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.