MECHANISM OF RENAL ACID-BASE HOMEOSTASIS

肾酸碱平衡机制

• 批准号: 3229559
• 负责人: THOMAS D DUBOSE
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229559
• 关键词: acid base balance; acidity /alkalinity; acidosis; aldosterone; amiloride; bicarbonates; carbon dioxide tension; carbonate dehydratase; homeostasis; hydrogen transport; kidney metabolism; kidney pharmacology; laboratory rat; lithium; microcalorimetry; microelectrodes; micropuncture; perfusion; renal tubular transport; renal tubule acidosis; respiratory acidosis

The primary objective of the studies outlined in this proposal is to elucidate more fully the overall role of the kidney in systemic acid-base homeostais. During previous years studies have been designed to investigate the basic mechanism(s) responsible for urinary acidification and the regulation of this process in several nephorn segments, the maintenance of elevated CO2 tensions in the renal cortex, and the utility of urinary COs tension as a qualitative index of H+ secretion by the terminal nephron. The present application proposes to continue our investigation of fundamental mechanisms of the acidification process, but places major emphasis on investigation of the mechanism of impaired urinary acidification in experimental models of deranged acid- base and/or electrolyte balance. In order to accomplish these goals four specific projects are proposed: 1) Evaluation of acidification parameters in experimental models of distal renal tubular acidosis and selective aldosterone deficiency. 2) Evaluation of segmental ammonia transport in medullary and cortical nephrons to determine the role of ammonia transfer from the loop of Henle to the collecting duct in urinary ammonium excretion during changes in systemic potassium balance, mineralocorticoid deficiency and ureteral obstruction. 3) Evaluation of the role of transepithelial pH gradients in the regulation of H+ secretion by the proximal convoluted tubule. 4) Evaluation of the mechanism and kinetics of H+ secretion in human brush border membrane vesicles in vitro and to compare these findings with other mammaliam species. An important advantage of the in vivo micropuncture studies proposed in this application is the capability in our laboratory of extending these observations by investigation similar questions in the isolated perfused tubule in vitro. The maintenance of acid-base balance is an essential physiological role of the kidney. The control of this process must be understood to fully elucidate these functions. The study of models of deranged acidification, such as renal tubular acidosis, may enhance our understanding of this disease in humans, and improve our ability to diagnose this condition early in the course of the disease.

该提案中概述的研究的主要目的是 更全面地阐明肾脏在系统性中的总体作用 酸碱稳态。 在过去的几年中 旨在研究负责的基本机制 尿酸化和几个过程的调节 Nephorn段，维持高架二氧化碳紧张局势 肾皮质，以及尿液cos张力的效用 末端肾单位的H+分泌定性指数。 这 目前的申请建议继续我们调查 酸化过程的基本机制，但位置 重点是调查受损机制 尿酸化在失去酸的实验模型中 基础和/或电解质平衡。 为了完成这些 目标提出了四个特定项目：1）评估 远端肾脏实验模型中的酸化参数 管状酸中毒和选择性醛固酮缺乏症。 2） 评估髓质中的分段氨运输 皮质肾单位确定氨转移的作用 Henle的循环到尿铵中的收集管道 全身钾平衡变化期间的排泄物， 矿物皮质激素缺乏和输尿管阻塞。 3） 评估thransepithelial pH梯度在 调节近端综合小管对H+分泌的调节。 4） 评估H+分泌的机制和动力学 人刷边框膜囊泡体外并进行比较 这些发现与其他哺乳动物物种。 一个重要的 在此提出的体内微源研究的优势 应用是我们实验室扩展这些功能的能力 通过调查观察孤立的问题 体外灌注小管。 酸碱平衡的维持是 肾脏的重要生理作用。 对此的控制 必须理解过程以充分阐明这些功能。 诸如肾脏酸化模型的研究 管状酸中毒可能会增强我们对这种疾病的理解 人类，并提高我们在早期诊断这种情况的能力 疾病的病程。