MECHANISMS OF PRESSURE NATRIURESIS IN PROXIMAL TUBULES

近端肾小管压力尿钠机制

• 批准号: 6141037
• 负责人: Kay-Pong Daniel Yip
• 金额: $ 18.42万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6141037
• 关键词: acidity /alkalinity; adenosinetriphosphatase; apical membrane; blood pressure; brush border membrane; confocal scanning microscopy; fluorescence microscopy; fluorescent dye /probe; hypertension; immunocytochemistry; intracellular transport; kidney imaging /visualization; membrane transport proteins; optics; protein transport; renal tubular transport; saluresis; spontaneous hypertensive rat; western blottings

The long-term goal of this proposed study is to identify the mechanisms of pressure natriuresis in proximal tubules and its relationship with hypertension. Pressure natriuresis is an increase of Na+ excretion caused by an increase in arterial pressure in the absence of changes in renal blood flow and glomerular filtration rate, which enables the kidney to use arterial pressure as an input signal to regulate the extracellular fluid volume. However, pressure natriuresis is set to higher blood pressure levels in all form of hypertension. An acute blood pressure increase inhibits fluid and NaC1 reabsorption in rate proximal tubules, and this response is associated with a rapid internalization of apical Na+/H+ exchangers from the brush border into subapical intracellular stores. This response probably contributes a large fraction of the natriuresis and diuresis that occurs when blood pressure rises. The objective of this proposal is to test whether trafficking of apical Na+/H+ exchangers induced by acute hypertension inhibits apical Na+/H+ exchangers activity and fluid reabsorption in proximal tubules in vivo, to delineate the mechanisms of this protein-trafficking process, and to probe the possible changers in hypertension. The rate of change in intracellular pH (dpHi/dt) upon luminal removal of Na+ in perfused proximal tubules in situ is used as a index of the activities of Na+/H+ exchangers. The intracellular pH is monitored with a dual pulse-lasers system designed to measure intracellular pH with minimum bleaching of BCECF, a pH sensitive fluorescence dye commonly-used to measure intracellular pH. Proximal fluid reabsorption is measured continuously with a non-obstructing optical technique developed in this laboratory. Confocal fluorescent microscopy and immunohistochemistry are employed to investigate the protein trafficking process triggered by acute hypertension. Spontaneously hypertensive rates (SHR) are used as an animal model of chronic hypertension. This proposed study will provide new information to understand the cellular mechanism of pressure natriuresis in proximal tubules, and the altered relationship between renal perfusion pressure and urinary Na+ excretion in hypertension. These may lead to a better understanding of the role of the kidney in hypertension, and possibly to new treatment principles.

这项拟议研究的长期目标是确定 近端小管及其的压力纳特里雷SIS机理 与高血压的关系。 压力纳特里雷斯是一种增加 由Na+排泄由动脉压的增加引起的 肾脏血流和肾小球滤过的没有变化 速率，这使肾脏能够使用动脉压作为输入 信号调节细胞外流体体积。 但是，压力 Natriuresis以所有形式的血压水平设置为较高的血压水平 高血压。 急性血压升高会抑制液体，并 NAC1近端小管的重吸收，此反应是 与顶端Na+/H+交换器的快速内在化相关 从刷子边界到亚皮细胞内存储。 这 响应可能会贡献很大一部分的纳地雷SIS和 血压升高时发生的利尿。 目的 该提议是测试贩运Na+/H+的贩运 急性高血压诱导的交换器抑制了顶端Na+/H+ 交换器的活性和流体在近端小管中的吸收 体内，描绘这种蛋白质贩运的机制 过程，并探测高血压的可能改变者。 这 腔内去除时细胞内pH（DPHI/DT）的变化速率 Na+在灌注近端小管原位被用作索引 NA+/H+交换器的活动。 监测细胞内pH 用双重脉冲激光系统设计用于测量细胞内pH 随着BCECF的最小漂白，pH敏感荧光染料 通常用于测量细胞内pH值。 近端流体 通过非启动光学的光接连续测量重吸收 该实验室开发的技术。 共聚焦荧光 使用显微镜和免疫组织化学来研究 急性高血压触发的蛋白质运输过程。 自发性高血压率（SHR）用作动物模型 慢性高血压。 这项拟议的研究将提供新的 了解压力的细胞机理 近端小管中的纳特里雷SIS，以及之间的关系改变 高血压中的肾脏灌注压力和尿Na+排泄。 这些可能会更好地理解肾脏在 高血压，甚至可能达到新的治疗原则。