Kiil F, Ostensen J
University of Oslo, Institute for Experimental Research, Ullevaal Hospital, Norway.
Acta Physiol Pharmacol Bulg. 1989;15(1):3-12.
In the proximal tubules, fractional reabsorption remains essentially unchanged during variations in glomerular filtration rate (GFR). Glomerulotubular balance (GTB), defined as the linear relationship between proximal tubular reabsorption and GFR, is quantitatively the most important regulator of tubular reabsorption, which may be stopped by inhibiting Na, K-ATPase activity completely. However, ouabain in doses inhibiting 80% of the Na, K-ATPases, exerts no effect on proximal reabsorption of water, NaCl and NaHCO3. At constant plasma pH, the same relationship between filtered and reabsorbed bicarbonate is obtained whether bicarbonate reabsorption is altered by varying GFR or plasma concentration of bicarbonate. In contrast, a selective rise in plasma NaCl concentration at constant plasma pH (hypernatremia) reduces NaHCO3 reabsorption and fails to stimulate NaCl reabsorption. Other characteristics of proximal tubular reabsorption are that nonreabsorbable solutes, such as mannitol, inhibit water and NaCl reabsorption with little or no change in NaHCO3 reabsorption and renal oxygen consumption. Mannitol reduces the slope of the GTB curve for NaCl but not for NaHCO3. Hypertonic NaHCO3 exerts an osmotic effect on proximal water and NaCl reabsorption comparable to that of mannitol, whereas hypertonic NaCl is without osmotic effect. By reducing plasma pH (hypercapnia at high plasma bicarbonate concentration), the slope of the GTB curves for NaCl and NaHCO3 can be greatly increased. By raising plasma pH either by hypocapnia or bicarbonate loading, proximal reabsorption of NaHCO3 and NaCl is greatly depressed and remains almost unaltered during variations of GFR (abolished GTB). Similarly, carbonic anhydrase inhibitors, such as acetazolamide, reduce the reabsorption of NaCl and NaHCO3 in the same proportion as a rise in plasma pH, and abolish GTB. Examinations of proximal tubular oxygen consumption indicate that the energy requirement for NaHCO3 reabsorption is as expected for transcellular transport by Na, K-ATPases, whereas proximal NaCl reabsorption requires no additional energy. These data indicate that transcellular energy-requiring NaHCO3 reabsorption provides the main osmotic force across the tight junction for paracellular reabsorption of proximal tubular fluid containing NaCl and other solutes of low reflection coefficient. The main factors influencing GTB are the filtered load of bicarbonate, plasma pH and nonreabsorbable solutes in the proximal tubular fluid.
在近端小管中，肾小球滤过率（GFR）变化时，分数重吸收基本保持不变。球管平衡（GTB）定义为近端小管重吸收与GFR之间的线性关系，从数量上看，它是肾小管重吸收最重要的调节因素，完全抑制钠钾ATP酶活性可使其停止。然而，哇巴因剂量抑制80%的钠钾ATP酶时，对水、氯化钠和碳酸氢钠的近端重吸收无影响。在血浆pH恒定的情况下，无论碳酸氢盐重吸收是因GFR变化还是血浆碳酸氢盐浓度变化而改变，滤过的碳酸氢盐与重吸收的碳酸氢盐之间都存在相同的关系。相反，在血浆pH恒定（高钠血症）时血浆氯化钠浓度选择性升高会降低碳酸氢钠重吸收，且不会刺激氯化钠重吸收。近端小管重吸收的其他特征是，不可重吸收的溶质，如甘露醇，抑制水和氯化钠重吸收，而碳酸氢钠重吸收和肾氧消耗几乎无变化。甘露醇降低了氯化钠的GTB曲线斜率，但未降低碳酸氢钠的GTB曲线斜率。高渗碳酸氢钠对近端水和氯化钠重吸收产生的渗透作用与甘露醇相当，而高渗氯化钠则无渗透作用。通过降低血浆pH（高血浆碳酸氢盐浓度时的高碳酸血症），氯化钠和碳酸氢钠的GTB曲线斜率可大幅增加。通过低碳酸血症或碳酸氢盐负荷使血浆pH升高时，碳酸氢钠和氯化钠的近端重吸收会大幅降低，且在GFR变化期间几乎保持不变（球管平衡消失）。同样，碳酸酐酶抑制剂，如乙酰唑胺，会使氯化钠和碳酸氢钠的重吸收按与血浆pH升高相同的比例降低，并消除球管平衡。对近端小管氧消耗的检测表明，碳酸氢钠重吸收的能量需求符合钠钾ATP酶跨细胞转运的预期，而近端氯化钠重吸收不需要额外能量。这些数据表明，跨细胞需能的碳酸氢钠重吸收为近端小管液中含氯化钠和其他反射系数低的溶质通过紧密连接进行的旁细胞重吸收提供了主要渗透力。影响球管平衡的主要因素是碳酸氢盐的滤过量、血浆pH和近端小管液中的不可重吸收溶质。
