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: 3232148
• 负责人: JACK WORK
• 金额: $ 11.2万
• 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/3232148
• 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.

该项目重点关注髓质间质钾的调节 和正常条件下的盐浓度 改变体内钾平衡和 ADH（加压素）水平。 研究将 利用灌注两种特定的分离管段的方法 患有糖尿病的无病原体 Sprague-Dawley 大鼠和 Brattleboro 大鼠 尿崩症。 尽管这些动物模型已被广泛研究 以前利用其他研究技术，应用 大鼠离体肾小管技术受到限制。 这个新的 开发将允许体外灌注结果的直接关联 与先前对同一物种的体内微穿刺​​的结果进行比较。 方法将涉及净离子通量和单向离子通量的测量 和跨上皮电压在孤立的、灌注的环路段中 亨利. 饮食和药物方案将用于发展慢性病 钾缺乏和慢性钾负荷，以及生理学 替代 Brattleboro 大鼠中的 ADH。 初步研究将检查 钾可能分泌到下行细胞的潜在机制 通过体内微穿刺​​观察到的亨利袢的肢体， 以及这些机制是否受到钾负荷的影响 已被证明可以极大地增加钾向尖端的输送 亨利环。 最近的证据还表明钾的运动 穿过粗升肢的顶膜与盐耦合 通过共同的运输机制吸收。 ADH对净盐的影响 控制检查髓质厚升肢的吸收 以及在缺钾的 Sprague-Dawley 大鼠中，以确定 低钾血症会导致注意力集中缺陷。 最后是布拉特尔伯勒 大鼠将被用作尿崩症模型，其尿崩症的减少 对外源性 ADH 的反应。 研究将检验抗利尿激素 (ADH) 对 钾转运；长期服用 AHD 与 髓质形态和吸盐率的变化 将检查粗的升肢。 这些研究的结果应该 扩大我们对钾和 ADH 相互关系的理解，并且 它们在调节健康和疾病中溶质转运的作用。