Bicarbonate as mediator of proximal tubular NaCl reabsorption and glomerulotubular balance

Abstract

To examine the role of bicarbonate as mediator of NaCl reabsorption, acetazolamide was administered in a small or conventional dose (30 mg/kg body wt) and a large dose (500 mg/kg body wt) to anaesthetized dogs during inhibition of distal NaCl reabsorption by ethacrynic acid. During saline infusion, ethacrynic acid reduced sodium reabsorption to 65 ± 2% and chloride reabsorption to 55 ± 2% of filtered load. The inhibitory effect of the large dose of acetazolamide was almost twice that of the small dose. At control glomerular filtration rate (GFR) the large dose reduced sodium reabsorption to 26 ± 2%, chloride reabsorption to 25 ± 1% and bicarbonate reabsorption to 18 ± 3% of filtered load. Both the small and the large dose of acetazolamide reduced the reabsorption of three sodium ions and two chloride ions per bicarbonate ion. After the large dose, bicarbonate, sodium and chloride reabsorption were constant at GFR between 25 and 100% of control, and glomerulotubular balance was therefore absent during variations in GFR within this range. The inhibitory effects of acetazolamide were greatly reduced by metabolic acidosis indicating that the large dose of acetazolamide did not inhibit NaCl reabsorption by mechanisms independent of bicarbonate reabsorption. Histochemical examination and direct measurements of enzyme activity showed that only the large dose of acetazolamide completely inhibited carbonic anhydrase activity. Hence, complete inhibition of carbonic anhydrase inhibits 80% of bicarbonate reabsorption and 40% of sodium reabsorption. We conclude that bicarbonate reabsorption is the main mediator of osmotic water and NaCl reabsorption and of glomerulotubular balance in the proximal tubules.

Key Words:

• acetazolamide
• carbonic anhydrase
• chloride reabsorption
• dogs
• ethacrynic acid
• glomerular filtration rate