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(可能是固有的 肾脏或对调节性体液药物的异常反应) 这会导致实验中不适当的钠滞留 高血压的动物模型。这背后的假设是 项目是推定的膜缺陷表示为 肾细胞的细胞内稳态紊乱， 因此，应该可以通过细胞内浓度检测到 测量。用于测定电解液浓度 在单个管状细胞，甚至亚细胞结构中，我们将 采用电子探针分析技术。这个 将对冷冻干燥的薄切片进行分析 从新鲜的、电击冷冻的组织样本中获得。最初，只有 短小的、未灌流的孤立肾单位段将被用作 样本。稍后，我们将尝试获取更长的细分市场 它可以在体外条件下冷冻之前进行灌流。 为此，我们将开发一种技术，使快速 肾小管在灌流过程中冻结。使用这些 方法，我们将首先研究细胞电解质的组成。 不同的管段从两个不同的 基因固定的高血压模型。第二，我们将 研究高和正常含NaCl日粮对小鼠的影响 不同的动物模型。第三，我们将调查 对调节剂的异常反应的可能性 肾小管钠转运。该项目将紧密结合在一起 与项目2、3、4和8的运输研究。

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.