灌注大鼠肾脏中钠离子重吸收与氧气及乳酸利用的关系。

Relation of Na+ reabsorption to utilization of O2 and lactate in the perfused rat kidney.

作者信息

Cohen J J, Merkens L S, Peterson O W

出版信息

Am J Physiol. 1980 May;238(5):F415-27. doi: 10.1152/ajprenal.1980.238.5.F415.

DOI:10.1152/ajprenal.1980.238.5.F415

Abstract

When the ratio delta TNa+/delta QO2 is used to estimate the energy requirements for net Na+ reabsorption (TNa+), it is assumed that the entire change in renal O2 uptake (delta QO2) is utilized only for the delta TNa+. However, if increases in renal synthetic work also occur when TNa+ is increased, the energy cost for TNa+ will be overestimated. We perfused the substrate-limited isolated rat kidney at 38 degrees C, pH 7.4, a mean arterial pressure of 120 mmHg, and mean lactate concentrations between 0 and 8.3 mM. We measured QO2, TNa+, net reabsorption of lactate (Tlac), net utilization of lactate (Qlac), lactate decarboxylation rate (Qlacox), as well as the net entry rate of lactate into biosynthetic pathways (Qxslac). When no exogenous substrate was present (rates are means, g wet wt-1 . min-1) GFR was 351 +/- 38 microliter, %TNa+ was 54 +/- 2%, and QO2 was 2.85 +/- 0.31 mumol; there was also a loss of about 20% of renal tissue K+ content. When mean [lactate] greater than or equal to 0.73 mM, the loss of tissue K+ was completely prevented and %TNa+ increased to and remained at about 85%. At mean [lactate] of 8.3 mM, Tlac was 5.1 +/- 0.6 mumol, QO2 was 6.12 +/- 1.24 mumol, and GFR was 709 +/- 83 microliter. Qlac, delta Qlacox and delta TNa+ increased in parallel with each other and approaches maximal rates as [lactate] was raised. By contrast, Tlac increased as a linear function of perfusate [lactate] and was not related to changes in Qlac. The molar increases in TNa+ were 10- to 20-fold greater than the increases in Tlac. It is more probable, therefore, that lactate enhances TNa+ by providing energy from its oxidation rather than by a co-transport phenomenon. At all concentrations of lactate, more lactate was utilized (Km = 1.2 mM; Vmax = 3.4) than was decarboxylated (Km = 1.6 mM; Vmax = 1.7), indicating that as lactate concentration increased, both the synthesis of new products from lactate and Na+ reabsorption increased. We conclude that the ratio delta TNa+/delta QO2, overestimates the energy cost of Na+ reabsorption. In order to obtain an accurate estimate of the energy requirements for TNa+ in kidney, the simultaneous changes in the rate of net biosynthetic work must also be quantified as TNa+ is changed.

摘要

当使用ΔTNa⁺/ΔQO₂的比值来估算净Na⁺重吸收（TNa⁺）的能量需求时，假定肾脏摄氧量的全部变化（ΔQO₂）仅用于ΔTNa⁺。然而，如果在TNa⁺增加时肾脏合成工作也增加，那么TNa⁺的能量消耗将被高估。我们在38℃、pH 7.4、平均动脉压120 mmHg以及平均乳酸浓度在0至8.3 mM之间的条件下，对底物受限的离体大鼠肾脏进行灌注。我们测量了QO₂、TNa⁺、乳酸的净重吸收（Tlac）、乳酸的净利用（Qlac）、乳酸脱羧速率（Qlacox）以及乳酸进入生物合成途径的净进入速率（Qxslac）。当不存在外源性底物时（速率为平均值，g湿重⁻¹·min⁻¹），肾小球滤过率（GFR）为351±38微升，TNa⁺百分比为54±2%，QO₂为2.85±0.31微摩尔；同时肾脏组织钾含量也损失了约20%。当平均[乳酸]≥0.73 mM时，组织钾的损失被完全阻止，TNa⁺百分比增加至约85%并保持在该水平。在平均[乳酸]为8.3 mM时，Tlac为5.1±0.6微摩尔，QO₂为6.12±1.24微摩尔，GFR为709±83微升。Qlac、ΔQlacox和ΔTNa⁺彼此平行增加，并随着[乳酸]升高接近最大速率。相比之下，Tlac随着灌注液[乳酸]呈线性函数增加，且与Qlac的变化无关。TNa⁺的摩尔增加量比Tlac的增加量大10至20倍。因此，更有可能的是，乳酸通过其氧化提供能量而非通过共转运现象来增强TNa⁺。在所有乳酸浓度下，被利用的乳酸（Km = 1.2 mM；Vmax = 3.4）比脱羧的乳酸（Km = 1.6 mM；Vmax = 1.7）更多，这表明随着乳酸浓度增加，由乳酸合成新产物以及Na⁺重吸收均增加。我们得出结论，ΔTNa⁺/ΔQO₂的比值高估了Na⁺重吸收的能量消耗。为了准确估算肾脏中TNa⁺的能量需求，在TNa⁺发生变化时，净生物合成工作速率的同时变化也必须进行量化。