Factors limiting renal proximal tubular reabsorption at high glomerular filtration rate

To examine the factors limiting proximal reabsorption, distal reabsorption was inhibited by continuous infusion of ethacrynic acid in anaesthetized dogs. During combined infusion of ethacrynic acid and 0.9% saline, autoregulation of renal blood flow is impaired and glomerular filtration rate (GFR) can be varied by lowering or raising renal perfusion pressure. During lowering of GFR reabsorption of bicarbonate, chloride and sodium varied in proportion to reduction in GFR (glomerulotubular balance), but during elevation of GFR the increase in the filtered load of all three ions was excreted and a maximal rate of reabsorption was approached. Administration of acetazolamide reduced the reabsorption of bicarbonate, chloride and sodium in the ratio 1:2:3, whether GFR was at control, reduced (74% of control) or increased (124% of control). Renal blood flow was 80--90% greater at high than at low GFR. These observations indicate that bicarbonate concentration increases along the proximal tubules during elevation of GFR, until plasma bicarbonate concentration is approached at the distal end of the proximal tubules. From then on, bicarbonate reabsorption cannot be further raised by increasing GFR. Proximal tubular sodium reabsoption reaches a maximum at high GFR because NaCl reabsorption varies in proportion to bicarbonate reabsorption.