ANGIOTENSIN EFFECTS IN HYPOTHALAMUS AND ADRENAL MEDULLA

血管紧张素II（AngII）是一种具有多种作用的强有力的介质 与心血管调节和体液平衡有关。 大量证据表明：1）血管紧张素受体可能 被分为两个或两个以上的亚型，和2）其他 血管紧张素II以外的血管紧张素肽可作用于血管紧张素 受体。 特别关注的是神经元效应 血管紧张素，但这种实验的解释已经证明， 由于相对快速的新陈代谢和低 脑内血管紧张素II的浓度。 这些限制强调 其他血管紧张素肽可能局部介导 一些作用显然由Ang II介导。 因此，研究 该提案旨在检验以下假设： 肾素-血管紧张素系统与两个或多个亚类的 神经元血管紧张素受体通过选择性产生两个或 更具有生理活性的血管紧张素肽。朝着这个 该提案将针对两个具体目标： 1)为了表征血管紧张素肽与 大鼠下丘脑-神经垂体系统对 精氨酸加压素释放; 2)为了表征血管紧张素肽与 大鼠肾上腺髓质控制肾上腺素的释放。 对于每一个具体目标，计划进行三组实验： 1)为了比较Ang 11、Ang-（2-8）和Ang-（2- 8）的相对效力， (1-7)促进荷尔蒙释放; 2)为了研究血管紧张素Ⅰ或血管紧张素Ⅱ对血管紧张素Ⅱ释放的影响， 在存在阻断血管紧张素的抑制剂的情况下的激素 肽酶; 3)直接评价这些肽酶抑制剂的作用 对组织中血管紧张素I或血管紧张素II代谢的影响。 此外，大脑的肾素-血管紧张素系统将 通过研究血管紧张素肽（Ang I， Ang-（2-8）和Ang-（1-7 下丘脑-神经垂体系统 从拟议的研究中获得的证据可能具有 关于治疗疾病的重大影响， 血管紧张素发挥作用，因为更好的表征 与血管紧张素肽相互作用的酶和受体 可能导致酶抑制剂和受体的发展 选择性地阻断所述受体的特定作用的拮抗剂， 血管紧张素系统

Angiotensin II (Ang II) is a potent mediator of numerous effects related to cardiovascular regulation and body fluid homeostasis. Substantial evidence indicates: 1) that angiotensin receptors may be classified into two or more subtypes, and 2) that other angiotensin peptides in addition to Ang II may act upon angiotensin receptors. Particular interest has focused on the neuronal effects of angiotensins, but interpretation of such experiments has proven difficult because of the relatively rapid metabolism and low concentration of Ang II in the brain. These limitations underscore the possibility that other angiotensin peptides may locally mediate some effects apparently mediated by Ang II. Thus, the research proposal is designed to test the following hypothesis: that the renin-angiotensin system interacts with two or more subclasses of neuronal angiotensin receptors via selective generation of two or more physiologically active angiotensin peptides. Toward this objective, the proposal will address two specific aims: 1) To characterize the interaction of angiotensin peptides with the rat hypothalamoneurohypophysial system in the control of arginine vasopressin release; 2) To characterize the interaction of angiotensin peptides with the rat adrenal medulla in the control of epinephrine release. For each specific aim, three sets of experiments nave been planned: 1) To compare the relative potencies of Ang 11, Ang-(2-8) and Ang- (1-7) in promoting hormonal release; 2) To study the effects of Ang I or Ang II on release of the hormone in the presence of inhibitors which block angiotensin peptidases; 3) To directly evaluate the effect of these peptidase inhibitors on the metabolism of Ang I or Ang II in the tissue. In addition, the renin-angiotensin system of the brain will be further tested by studying release of angiotensin peptides (Ang I, Ang II, Ang-(2-8), and Ang-(1-7)) from the in vitro perifused hypothalamo-neurohypophysial system. The evidence obtained from the proposed studies may have significant implications concerning the treatment of diseases in which angiotensin plays a role, since better characterization of the enzymes and receptors which interact with angiotensin peptides could lead to the development of enzyme inhibitors and receptor antagonists which selectively block particular effects of the renin-angiotensin system.