INTERACTIONS BETWEEN ANGIOTENSIN II AND NOREPINEPHRINE

血管紧张素 II 和去甲肾上腺素之间的相互作用

• 批准号: 3897611
• 负责人: L GABRIEL NAVAR
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3897611
• 关键词: angiotensin II; cell membrane; hormone regulation /control mechanism; juxtaglomerular apparatus; kidney cell; laboratory rat; micropuncture; neurotransmitters; norepinephrine; physical chemical interaction; renal tubular transport

It has been suggested that subtle humoral interactions may influence kidney function to enhance tubular reabsorption of fluid and electrolytes inappropriately in some types of hypertension. In essence, normal kidneys may respond appropriately to abnormally elevated levels of sodium- retaining hormones. Thus, inappropriate sodium conservation may result as a consequence of multiple and perhaps synergistic influences on various segments of the nephron. This project will specifically consider potential interactions between the reabsorptive influences of angiotensin II and catecholomines at the level of the proximal tubule. The basis for this approach is that hypertension in patients and/or experimental models has been associated with either elevated sympathetic neural activity or enhanced activity of the renin-angiotensin system or both. The main objectives of this project are to determine if angiotensin II and norepinephrine act in an additive or synergistic manner to enhance proximal tubule reabsorptive rate and to evaluate the cellular transport mechanisms mediating these effects. In accord with these objectives, we have the following specific aims: 1. To determine if, under in vivo experimental conditions, increases in peritubular concentrations of angiotensin II and norepinephrine above the endogenous levels exert synergistic effects on proximal tubule reabsorptive function. 2. To establish the effects of angiotensin II and norepinephrine, both individually and in combination, on proximal tubule reabsorptive function of the blood-perfused juxtamedullary nephron preparation. 3. To delineate the cellular mechanisms mediating the effects of angiotensin II and norepinephrine on proximal tubule cell transport function and determine if these mechanisms are interactive. These three main specific aims will be approach using three different experimental techniques: in vivo micropuncture and microperfusion, the blood-perfused juxtamedullary nephron preparation, and isolated proximal tubular cells.

有人认为，微妙的幽默互动可能会 影响肾功能促进肾小管重吸收 液体和电解质不适当地存在于某些类型的 高血压。从本质上讲，正常的肾脏可能会对 适当地保持异常高的钠含量 荷尔蒙。因此，可能会导致不适当的钠守恒。 由于多重的，也许是协同的影响的结果 在肾单位的不同节段。这个项目将 具体考虑两个组件之间的潜在交互作用 血管紧张素II和儿茶酚胺对血管再吸收的影响 近端小管的水平。这种方法的基础是 患者和/或实验模型中的高血压 要么与交感神经活性升高有关 或者肾素-血管紧张素系统的活性增强，或者两者兼而有之。 该项目的主要目标是确定 血管紧张素II和去甲肾上腺素以相加或协同作用的方式起作用 提高近端肾小管重吸收率的方法 评估介导这些变化的细胞传输机制 效果。与这些目标相一致，我们有以下几点 具体目标： 1.确定在活体实验条件下， 肾小管周围血管紧张素II和血管紧张素Ⅱ浓度升高 去甲肾上腺素在内源性水平以上发挥协同作用 对近曲小管再吸收功能的影响。 2.为了确定血管紧张素II和去甲肾上腺素的作用， 在近端小管上，单独和联合使用 血液灌流延髓旁的再吸收功能 肾单位准备。 3.阐明调控效应的细胞机制 血管紧张素II和去甲肾上腺素对近端肾小管细胞的影响 传输功能，并确定这些机制是否 互动性。 这三个主要的具体目标将使用三个 不同的实验技术：体内微穿刺法和 微灌注，血液灌流的延髓旁肾单位 制备，分离近端肾小管上皮细胞。