ION TRANSPORT REGULATION IN ISOLATED RAT RENAL TUBULES

离体大鼠肾小管中离子传输的调节

• 批准号: 3232149
• 负责人: JACK WORK
• 金额: $ 11.82万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232149
• 关键词: diabetes insipidus; disease /disorder model; genetic strain; hormone regulation /control mechanism; hypokalemia; ion transport; mathematical model; model design /development; perfusion; renal tubular transport; salts; secretion; vasopressins

This project focuses on the regulation of medullary interstitial potassium and salt concentrations under normal conditions and in the presence of altered body potassium balance and ADH (vasopressin) levels. Studies will utilize the method of perfusing isolated tubule segments of both specific pathogen-free Sprague-Dawley rats and Brattleboro rats with diabetes insipidus. Although these animal models have been extensively studied previously utilizing other research techniques, the application of the isolated tubule technique in the rat has been limited. This new development will allow direct correlation of results of in vitro perfusion with previous results from in vivo micropuncture of the same species. Methodologies will involve measurement of net and unidirectional ion fluxes and transepithelial voltages in isolated, perfused segments of the loop of Henle. Dietary and drug protocols will be used to develop chronic potassium depletion and chronic potassium loading, as well as physiologic replacement of ADH in the Brattleboro rat. Initial studies will examine potential mechanisms whereby potassium may be secreted into the descending limb of the loop of Henle as has been observed by in vivo micropuncture, and whether any of these mechanisms are affected by potassium loading which has been shown to greatly augment the delivery of potassium to the tip of the loop of Henle. Recent evidence also indicates that potassium movement across the apical membrane of the thick ascending limb is coupled to salt absorption by a common transport mechanism. The effect of ADH on net salt absorption in the medullary thick ascending limb will be exmined in control and in potassium-depleted Sprague-Dawley rats in order to define ways in which hypokalemia leads to concentrating defects. Finally the Brattleboro rat will be used as a model of diabetes insipidus with dimiminished responsiveness to exogenous ADH. Studies will examine the effect of ADH on potassium transport; correlations between chronic administration of AHD and changes in the morphology and rate of salt absorption in the medullary thick ascending limb will be examined. The results of these studies should expand our understanding of the interrelationship of potassium and ADH, and their role in regulating solute transport in health and disease.

本项目主要研究延髓间质钾的调节 和盐浓度在正常条件下，并在存在 改变身体钾平衡和ADH（加压素）水平。 研究将 利用灌注两种特异性的分离的小管段的方法， 无病原体Sprague-Dawley大鼠和糖尿病Brattleboro大鼠 尿崩症 虽然这些动物模型已经被广泛研究 以前利用其他研究技术，应用 在大鼠中的离体小管技术受到限制。 这个新 发展将允许直接相关的结果，在体外灌注 与以前相同物种体内显微穿刺的结果一致。 方法将涉及净离子通量和单向离子通量的测量 和离体的，灌注的环段的跨上皮电压， 亨利 饮食和药物方案将用于开发慢性 钾缺乏和慢性钾负荷，以及生理性 替代布拉特伯勒大鼠的ADH。 初步研究将审查 钾可能被分泌到下行神经系统的潜在机制 如通过体内显微穿刺观察到的Henle袢的分支， 以及这些机制中的任何一种是否受到钾负荷的影响， 已经显示出极大地增加了钾向尖端的输送， 亨利氏环 最近的证据也表明钾的运动 穿过粗的上升支的顶膜与盐偶联 通过共同的运输机制吸收。 ADH对净盐的影响 将在控制下清除髓厚升支中的吸收 以及钾耗竭的Sprague-Dawley大鼠，以确定 低钾血症会导致注意力不集中 最后是布拉特伯勒 大鼠将用作尿崩症模型， 对外源性ADH的反应。 研究将检查ADH对 钾转运; AHD长期给药与 延髓中盐吸收的形态和速率的变化 将检查粗的上行支。 这些研究的结果应该 扩大我们对钾和ADH相互关系的理解， 它们在调节健康和疾病中的溶质转运中的作用。