RENAL TUBULAR PC02 AND ACID-BASE EQUILIBRIUM

肾小管 PC02 和酸碱平衡

• 批准号: 3227994
• 负责人: F JOHN GENNARI
• 金额: $ 12.27万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227994
• 关键词: acid base balance; bicarbonates; carbon dioxide tension; computer simulation; epithelium; ion transport; ionophores; kidney metabolism; mathematical model; membrane model; microelectrodes; micropuncture; oxygen consumption; renal tubular transport

The proposed research is designed to gain insight into the process of CO2 transfer in the kidney cortex, and into the role of bicarbonate reabsorption in the early proximal tubule in the maintenance of acid-base equilibrium. Micropuncture and microelectrode measurements in rats will be coupled with mathematical modelling efforts to test specific hypotheses concerning: 1) the high PCO2 levels in the superficial renal cortex, 2) the influence of tubular bicarbonate and CO2 reabsorption on peritubular capillary PCO2, 3) the factors producing a transepithelial PCO2 gradient confined to the early proximal tubule, and 4) the factor influencing bicarbonate reabsorption along the proximal tubule. For each of these problems a mathematical model has been developed, based on physicochemical interactions between CO2, bicarbonate and hydrogen ions, and on the interaction of these species with-blood buffers. The models also consider the permeabilities and diffusivities of these species in their movement from one compartment to another. The assumptions used to develop the models will be tested by specific experimental maneuvers in Munich-Wistar rats designed to produce measurable changes in renal cortical PCO2. These experiments include acute plasma expansion, metabolic and respiratory acid-base disorders, carbonic anhydrase inhibition, inhibition or uncoupling of metabolic CO2 production, and diuretic administration. In these experiments, microelectrode PCO2 measurements as well as measurements of bicarbonate reabsorption will be carried out. Experimental PCO2 measurements will be compared with values calculated by the models for each setting to test specific hypotheses concerning CO2 and bicarbonate transfer from the tubular lumen to the peritubular capillaries. A separate group of experiments will focus on defining the factors influencing bircarbonate reabsorption in the first 1-2 mm of the proximal tubule. The effect of pH, filtered bicarbonate load, and transport inhibitors will be examined in micropuncture and microperfusion studies. Finally, we plan to measure Na+/H+ exchange activity in brush border membrane vesicles isolated from rat renal cortex. These studies should provide insight into the regulation of normal acid-base equilibrium, and ultimately into clinical disorders of acid-base equilibrium.

这项拟议的研究旨在深入了解二氧化碳的过程。 在肾皮质转移，并转化为碳酸氢盐的作用 近端小管早期重吸收在酸碱维持中的作用 均衡。将对大鼠进行微穿刺法和微电极测量 再加上检验特定假说的数学建模工作 涉及：1)浅层肾皮质二氧化碳分压水平高，2) 肾小管碳酸氢盐和二氧化碳重吸收对肾小管周围的影响 毛细血管二氧化碳分压，3)产生跨上皮二氧化碳分压梯度的因素 局限于早期近端小管；4)影响因素 碳酸氢盐沿近端小管重吸收。对于其中的每一个 根据物理化学原理，建立了数学模型。 二氧化碳、重碳酸盐和氢离子之间的相互作用，以及在 这些物种与血液缓冲液的相互作用。这些模型还考虑到 这些物种在运动过程中的渗透率和扩散率 从一个隔间到另一个隔间。 用于开发模型的假设将由特定的 慕尼黑-Wistar大鼠的实验动作设计为产生可测量的 肾皮质二氧化碳分压的变化。这些实验包括急性血浆 扩张性、代谢性和呼吸性酸碱紊乱 脱水酶抑制、代谢二氧化碳产生的抑制或解偶联， 和利尿剂的管理。在这些实验中，微电极PCO2 碳酸氢盐重吸收的测量和测量将是 被执行。实验测量的二氧化碳将与数值进行比较。 由每种设置的模型计算，以检验特定假设 关于二氧化碳和碳酸氢盐从管腔到管腔的转移 肾小管周围毛细血管。 另一组实验将集中于确定这些因素 影响牙周近端前1-2 mm重吸收的因素 小管。PH值、过滤后的碳酸氢盐负荷和运输的影响 将在微穿刺法和微灌注法研究中检查抑制剂。 最后，我们计划测量灌木丛边缘的Na+/H+交换活性 从大鼠肾皮质分离出膜泡。这些研究应该 提供对正常酸碱平衡调节的洞察，以及 最终转化为临床酸碱平衡紊乱。