ANGIOTENSIN EFFECTS IN HYPOTHALAMUS AND ADRENAL MEDULLA

血管紧张素II(Ang II)是一种强大的多种作用的介体 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 被分为两个或多个子类型，以及2)另一个 血管紧张素II以外的血管紧张素肽可能作用于血管紧张素 感受器。特别的兴趣集中在神经元效应上。 血管紧张素，但对这种实验的解释已经证明 难度较大，因为新陈代谢较快，且较低 脑内血管紧张素Ⅱ的浓度。这些限制突显了 其他血管紧张素肽局部介导的可能性 一些效应显然是由Ang II介导的。因此，这项研究 该提案旨在测试以下假设： 肾素-血管紧张素系统与两个或多个亚类的相互作用 神经性血管紧张素受体通过选择性地产生两个或两个或 生理活性更强的血管紧张素肽。朝向这个方向 为了实现这一目标，该提案将涉及两个具体目标： 1)研究血管紧张素与血管紧张素的相互作用 大鼠下丘脑-神经-垂体系统在控制 精氨酸加压素释放； 2)研究血管紧张素与血管紧张素的相互作用 控制大鼠肾上腺髓质中肾上腺素的释放。 针对每个具体目标，计划了三组实验： 1)比较Ang 11、Ang-(2-8)和Ang-(2-8)的相对位势。 (1-7)促进激素释放； 2)研究血管紧张素转换酶I和血管紧张素转换酶II对血管内皮细胞释放的影响 存在阻断血管紧张素的抑制剂时的激素 多肽酶； 3)直接评价这些多肽酶抑制剂的作用。 血管紧张素I或血管紧张素II在组织中的代谢。 此外，大脑的肾素-血管紧张素系统将 通过研究血管紧张素释放多肽(Ang I， Ang II、Ang-(2-8)和Ang-(1-7))从体外灌流 下丘脑-神经-垂体系统。 从拟议的研究中获得的证据可能有 对中国疾病治疗的重大影响 血管紧张素在其中起作用，因为更好地描述了 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 选择性阻断血管紧张素转换酶的特殊作用的拮抗剂 肾素-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.