RENAL TUBULAR PC02 AND ACID-BASE EQUILIBRIUM

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 重吸收在早期近端小管在维持酸碱 均衡 将在大鼠中进行微穿刺和微电极测量。 再加上数学建模的努力，以测试特定的假设， 关于：1）浅表肾皮质中的高PCO 2水平，2） 肾小管碳酸氢盐和CO_2重吸收对肾小管周围神经的影响 毛细血管PCO 2，3）产生跨上皮PCO 2梯度的因素 局限于早期近端小管，和4）影响因素 碳酸氢盐重吸收沿着近端小管。 为每个这些 问题的数学模型已经开发，基于物理化学 CO2、碳酸氢根和氢离子之间的相互作用，以及 这些物质与血液缓冲液的相互作用。 模型还考虑 这些物质在运动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 在Munich-Wistar大鼠中进行实验操作，旨在产生可测量的 肾皮质PCO 2的变化。 这些实验包括急性血浆 扩张、代谢和呼吸性酸碱失衡、碳酸 脱水酶抑制、代谢CO2产生的抑制或解偶联， 和利尿剂给药。 在这些实验中，微电极PCO 2 测量以及碳酸氢盐重吸收的测量将是 贯彻 将实验PCO 2测量值与 由模型为每种设置计算，以测试特定假设 关于CO2和碳酸氢盐从管腔转移到 管周毛细血管 一组单独的实验将集中于定义这些因素 影响近端前1-2 mm的碳酸氢盐重吸收 小管 pH值、过滤的碳酸氢盐负荷和运输的影响 将在微穿刺和微灌注研究中检查抑制剂。 最后，我们计划测量刷状缘中的Na+/H+交换活动， 从大鼠肾皮质分离的膜囊泡。 这些研究应 提供对正常酸碱平衡调节的深入了解， 最终导致临床酸碱平衡紊乱。

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.