Wang T, Egbert A L, Aronson P S, Giebisch G
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8026, USA.
Am J Physiol. 1998 Jun;274(6):F1015-9. doi: 10.1152/ajprenal.1998.274.6.F1015.
In metabolic acidosis, the capacity of the proximal tubule for bicarbonate absorption is enhanced, whereas NaCl reabsorption is inhibited. Recent evidence indicates that transcellular NaCl absorption in the proximal tubule is mediated by apical membrane Cl/formate exchange and Cl/oxalate exchange, in parallel with recycling of these organic anions. We evaluated whether the effect of metabolic acidosis to inhibit NaCl reabsorption in the proximal tubule is due at least in part to inhibition of organic anion-dependent NaCl transport in this nephron segment. Absorption rates of bicarbonate (JHCO3), chloride (JCl), and fluid (Jv) were measured in rat proximal tubule segments microperfused in situ. We confirmed that metabolic acidosis stimulates JHCO3 in tubules microperfused with 25 mM HCO3, pH 7.4. For measurements of JCl, tubules were microperfused with a low-bicarbonate (5 mM), high-chloride solution, simulating conditions in the late proximal tubule. Under these conditions, baseline JCl and Jv measured in the absence of formate and oxalate were not significantly different between control and acidotic rats. However, whereas addition of 50 ¿M formate or 1 ¿M oxalate to luminal and capillary perfusates markedly stimulated JCl and Jv in control rats, formate and oxalate failed to stimulate JCl and Jv in acidotic rats. We conclude that metabolic acidosis markedly downregulates organic anion-stimulated NaCl absorption, thereby allowing differential regulation of proximal tubule NaHCO3 and NaCl transport.
在代谢性酸中毒时，近端小管重吸收碳酸氢根的能力增强，而氯化钠的重吸收受到抑制。最近的证据表明，近端小管中跨细胞的氯化钠重吸收是由顶膜氯离子/甲酸根交换和氯离子/草酸根交换介导的，同时伴随着这些有机阴离子的循环利用。我们评估了代谢性酸中毒抑制近端小管氯化钠重吸收的作用是否至少部分归因于该肾单位节段中有机阴离子依赖性氯化钠转运的抑制。在原位微灌注的大鼠近端小管节段中测量了碳酸氢根（JHCO3）、氯离子（JCl）和液体（Jv）的吸收率。我们证实，代谢性酸中毒可刺激用25 mM HCO3、pH 7.4微灌注的小管中的JHCO3。为了测量JCl，用低碳酸氢根（5 mM）、高氯离子溶液对小管进行微灌注，模拟近端小管后期的情况。在这些条件下，在对照大鼠和酸中毒大鼠中，在不存在甲酸根和草酸根的情况下测量的基线JCl和Jv没有显著差异。然而，虽然向管腔和毛细血管灌注液中添加50 μM甲酸根或1 μM草酸根可显著刺激对照大鼠的JCl和Jv，但甲酸根和草酸根未能刺激酸中毒大鼠的JCl和Jv。我们得出结论，代谢性酸中毒显著下调有机阴离子刺激的氯化钠重吸收，从而允许对近端小管碳酸氢钠和氯化钠转运进行差异调节。
