CELLULAR ION HOMEOSTASIS IN HYPERTENSION

这个项目的目标是确定一种可能的 肾小管转运异常(肾脏固有的或 对调节性体液制剂的异常反应)，导致 实验性高血压动物模型中不适当的钠滞留 高血压。这个项目背后的假设是，假设 膜缺陷表现为细胞内稳态的紊乱。 因此，应该可以被细胞内检测到 浓度测量。用于电解液的测定 在单个肾小管细胞，甚至亚细胞结构中的浓度， 我们将采用电子探针分析技术。这些分析 将在冷冻干燥的薄切片上进行， 电击冷冻的组织样本。最初，只有短暂的、未灌流的孤立 取肾单位段作为标本。稍后，我们将尝试 获得较长的节段，在冷冻之前可以在In 体外条件。为此，我们将开发一种技术， 允许在灌流时快速冻结小管。使用这些 方法，我们将首先研究细胞电解质的组成。 从两种不同模型获得的不同管段 基因固定的高血压。第二，我们将考察高利率的影响 以及在不同动物模型中正常的含NaCl日粮。第三，我们 将调查异常反应的可能性 肾小管钠转运的调节器。这个项目将密切关注 与项目2、3、4和8的运输研究相结合。

The goal of this project is to identify the cellular basis of a likely tubular transport abnormality (either intrinsic to the kidney or an abnormal response to regulatory humoral agents) which leads to inappropriate sodium retention in experimental animal models of hypertension. The assumption underlying this project is that the presumed membrane defect is expressed in a disturbance of the cellular homeostasis of renal cells and, therefore, should be detectable by intracellular concentration measurements. For determination of electrolyte concentrations in individual tubular cells, or even subcellular structures, we will employ the technique of electron microprobe analysis. The analyses will be performed on thin frozen-dried cryosections obtained from fresh, shock-frozen tissue samples. Initially, only short, non-perfused isolated nephron segments will be used as specimen. Later, we will attempt to obtain longer segments which can be perfused prior to freezing under in vitro conditions. For this purpose, we will develop a technique which allows rapid freezing of the tubules while being perfused. Using these methods, we will first study the cellular electrolytes composition of different tubular segments obtained from two different models of genetically fixed hypertension. Second, we will examine the effect of high and normal NaC1-containing diets in different animal models. Third, we will investigate the possibility of an abnormal responsiveness to modulators of tubular Na transport. This project will be closely integrated with the transport studies of Projects 2, 3, 4 and 8.