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: 3855119
• 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/3855119
• 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，微妙的体液相互作用可能 影响肾功能增强肾小管重吸收 液体和电解质不适当地在某些类型的 高血压 从本质上讲，正常的肾脏可能会对 与异常升高的钠保留水平相适应 荷尔蒙 因此，不适当的钠保存可能会导致 由于多重的，也许是协同的影响， 在肾单位的各个部分。 该项目将 特别考虑了 血管紧张素II和儿茶酚胺的重吸收影响. 近端小管的水平。 这种方法的基础是 高血压患者和/或实验模型 与交感神经活动的增强有关 或增强的肾素-血管紧张素系统活性或两者。 本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 增强近端小管重吸收率和 评估细胞运输机制介导这些 方面的影响. 根据这些目标，我们有以下雅阁 具体目标： 1. 为了确定在体内实验条件下， 肾小管周围血管紧张素II浓度增加， 去甲肾上腺素在内源性水平以上发挥协同作用 影响近端小管重吸收功能。 2. 为了确定血管紧张素II和去甲肾上腺素的作用， 单独或联合作用于近端小管 血液灌流延髓的重吸收功能 肾单位制备。 3. 阐明介导这些效应的细胞机制 血管紧张素II和去甲肾上腺素对近曲小管细胞的影响 运输功能，并确定这些机制是否 互动 这三个主要的具体目标将采用三种方法 不同的实验技术： 体内微穿刺， 微灌注，血液灌注的延髓肾单位 制备和分离的近端肾小管细胞。