INTERACTIONS BETWEEN ANGIOTENSIN II AND NOREPINEPHRINE

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 某些类型的液体和电解质不适当 高血压。 从本质上讲，正常的肾脏可能会做出反应 适当地调节钠潴留水平异常升高 荷尔蒙。 因此，不适当的钠保存可能会导致 作为多重影响或协同影响的结果 分布于肾单位的各个部分。 该项目将 特别考虑之间的潜在相互作用 血管紧张素 II 和儿茶酚胺的重吸收影响 近曲小管的水平。 这种方法的基础是 患者和/或实验模型中的高血压 与交感神经活动升高有关 或增强肾素-血管紧张素系统的活性或两者兼而有之。 该项目的主要目标是确定是否 血管紧张素II和去甲肾上腺素以相加或协同的方式起作用 提高近曲小管重吸收率的方法 评估介导这些的细胞运输机制 影响。 根据这些目标，我们有以下目标 具体目标： 1. 确定在体内实验条件下，是否 血管紧张素 II 的肾小管周围浓度增加 高于内源性水平的去甲肾上腺素发挥协同作用 对近曲小管重吸收功能的影响。 2. 确定血管紧张素 II 和去甲肾上腺素的作用， 单独或组合，在近端小管上 血液灌注近髓的重吸收功能 肾单位准备。 3. 描述介导影响的细胞机制 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。 这三个主要具体目标将通过以下三个方面来实现 不同的实验技术：体内微穿刺和 微灌注，血液灌注的近髓肾单位 制备和分离近端肾小管细胞。

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.