CELLULAR ION HOMEOSTASIS IN HYPERTENSION

这个项目的目标是确定一个可能的细胞基础， 肾小管转运异常（肾脏固有的或 对调节性体液因子的异常反应）， 实验动物模型中不适当的钠潴留 高血压 这个项目的基本假设是， 膜缺陷表现为细胞内稳态的紊乱 因此，应该可以通过细胞内 浓度测量。 用于电解质测定 浓度在个别肾小管细胞，甚至亚细胞结构， 我们将采用电子探针分析技术。 的分析 将在从新鲜的， 冷冻组织样本 最初，只有短的，非灌注的孤立 将使用肾单位片段作为标本。 稍后，我们将尝试 获得更长的节段，其可以在冷冻之前灌注， 体外条件 为此，我们将开发一种技术， 允许在灌注时快速冷冻小管。 使用这些 方法，我们将首先研究细胞电解质组成， 从两个不同的模型获得的不同的管段， 遗传性高血压 第二，我们将研究高 在不同的动物模型中正常的含NaCl的饮食。 三是 将调查异常反应的可能性， 肾小管Na转运的调节剂。 该项目将密切 与项目2、3、4和8的运输研究结合。

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.