Hilden S A, Johns C A, Madias N E
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts.
Am J Physiol. 1989 Oct;257(4 Pt 2):F615-22. doi: 10.1152/ajprenal.1989.257.4.F615.
We have examined the activity and kinetic characteristics of the Na+-H+ exchanger in renal cortical brush-border membrane vesicles (BBMV) prepared from rabbits adapted to chronic hypocapnia in order to address whether this transporter might contribute to the suppressed proximal bicarbonate reabsorption characteristic of this disorder. Chronic hypocapnia was induced by exposing animals to 9% O2 for a 5-day period. In comparison with paired, contemporaneous controls, an average delta PaCO2 of 13 mmHg and an average delta [HCO3-] of 7.3 meq/l were obtained. Chronic hypocapnia led to a significant suppression of the 22Na+ uptake by BBMV; at the 3-s mark, a 30% suppression was observed (chronic hypocapnia, 4.05 +/- 0.43 nmol/mg protein; control, 5.72 +/- 0.39 nmol/mg protein) (P less than 0.01). A significant decrease in the Vmax of the antiporter was noted (chronic hypocapnia, 622.7 +/- 86.8 nmol.mg protein-1.min-1; control 857.5 +/- 64.8 nmol.mg protein-1.min-1) (P less than 0.01), whereas the Km for sodium remained unaltered. The specificity of this adaptation was supported by showing that Na+-dependent uptake of D-[3H]glucose by BBMV was not significantly different between chronic hypocapnia and control. Chronic normocapnic hypoxemia left Na+-H+ exchange activity undisturbed. We conclude that the observed change in the BBMV Na+-H+ antiporter might be responsible, at least in part, for the suppressed renal bicarbonate reabsorption characteristic of chronic hypocapnia and that a consequence of the hypocapnic state itself mediates this adaptation.
我们检测了从适应慢性低碳酸血症的家兔制备的肾皮质刷状缘膜囊泡（BBMV）中Na⁺-H⁺交换体的活性和动力学特征，以探讨该转运体是否可能导致这种疾病特征性的近端碳酸氢盐重吸收受抑制。通过将动物暴露于9% O₂ 5天来诱导慢性低碳酸血症。与配对的同期对照相比，平均ΔPaCO₂为13 mmHg，平均Δ[HCO₃⁻]为7.3 meq/l。慢性低碳酸血症导致BBMV对²²Na⁺摄取的显著抑制；在3秒时，观察到30%的抑制（慢性低碳酸血症组，4.05±0.43 nmol/mg蛋白质；对照组，5.72±0.39 nmol/mg蛋白质）（P<0.01）。发现反向转运体的Vmax显著降低（慢性低碳酸血症组，622.7±86.8 nmol·mg蛋白质⁻¹·min⁻¹；对照组，857.5±64.8 nmol·mg蛋白质⁻¹·min⁻¹）（P<0.01），而钠的Km保持不变。通过显示慢性低碳酸血症组和对照组之间BBMV对D-[³H]葡萄糖的钠依赖性摄取无显著差异，支持了这种适应性的特异性。慢性正常碳酸血症性低氧血症使Na⁺-H⁺交换活性不受影响。我们得出结论，观察到的BBMV中Na⁺-H⁺反向转运体的变化可能至少部分地导致了慢性低碳酸血症特征性的肾碳酸氢盐重吸收受抑制，并且低碳酸血症状态本身的一个后果介导了这种适应性。
