Dietary HCO3 reduces distal tubule acidification by increasing cellular HCO3 secretion.

We examined the components of net HCO3 reabsorption (H+/HCO3 secretion and transepithelial HCO3 permeability) in in vivo perfused distal tubules of anesthetized rats to determine the mechanisms by which dietary HCO3 reduces acidification in this nephron segment. Animals eating a minimum electrolyte diet drank either (in mM) 80 NaHCO3, 80 NaCl, or 40 Na2SO4 for 7-10 days and were compared with controls drinking distilled H2O. On perfusion with a HCO3- and Cl- -containing solution, net HCO3 reabsorption was lower than control in only the NaHCO3 animals (14.4 +/- 1.3 vs. 4.1 +/- 0.5 pmol.mm-1.min-1, P < 0.001). On perfusion with a 0 HCO3-0 Cl- solution, distal tubule luminal HCO3 accumulation (JHCO3) was higher in NaHCO3 animals than control (-13.7 +/- 1.3 vs. -4.7 +/- 0.7 pmol.mm-1.min-1, P < 0.002). Despite a higher JHCO3, estimated transepithelial HCO3 permeability in the NaHCO3 animals was similar to control [0.52 +/- 0.06 vs. 0.36 +/- 0.04 x 10(-7) cm2/s, P = not significant (NS)]. Luminal acetazolamide (Az) reduced JHCO3 in NaHCO3 animals to a level similar to control (-6.2 +/- 0.6 vs. -4.0 +/- 0.5 pmol.mm-1.min-1, P = NS) in this nephron segment containing cells with cytoplasmic but no luminal carbonic anhydrase activity. Including Cl- in the initial perfusate increased JHCO3 in NaHCO3 animals only (-20.8 +/- 1.9 vs. -13.7 +/- 1.3 pmol.mm-1.min-1, P < 0.02), and this increase was inhibited by luminal Az. Calculated H+ secretion was similar among groups. Together, the data indicate that dietary HCO3 reduces distal tubule acidification by increasing Az-sensitive generation of HCO3 by distal tubule cells that enters the lumen by a mechanism augmented by luminal Cl-.