T. Wang et al., EFFECT OF METABOLIC-ACIDOSIS ON NACL TRANSPORT IN THE PROXIMAL TUBULE, American journal of physiology. Renal, fluid and electrolyte physiology, 43(6), 1998, pp. 1015-1019
In metabolic acidosis, the capacity of the proximal tubule for bicarbo
nate absorption is enhanced, whereas NaCl reabsorption is inhibited. R
ecent evidence indicates that transcellular NaCl absorption in the pro
ximal tubule is mediated by apical membrane Cl-/formate exchange and C
l-/oxalate exchange, in parallel with recycling of these organic anion
s. We evaluated whether the effect of metabolic acidosis to inhibit Na
Cl reabsorption in the proximal tubule is due at least in part to inhi
bition of organic anion-dependent NaCl transport in this nephron segme
nt. Absorption rates of bicarbonate (J(HCO3)), chloride (J(Cl)), and f
luid (J(v)) were measured in rat proximal tubule segments microperfuse
d in situ. We confirmed that metabolic acidosis stimulates J(HCO3) in
tubules microperfused with 25 mM HCO3-, pH 7.4. For measurements of J(
Cl), tubules were microperfused with a low-bicarbonate (5 mM), high-ch
loride solution, simulating conditions in the late proximal tubule. Un
der these conditions, baseline J(Cl) and J(v) measured in the absence
of formate and oxalate were not significantly different between contro
l and acidotic rats. However, whereas addition of 50 mu M formate or 1
mu M oxalate to luminal and capillary perfusates markedly stimulated
J(Cl) and J(v) in control rats, formate and oxalate failed to stimulat
e J(Cl) and J(v) in acidotic rats. We conclude that metabolic acidosis
markedly downregulates organic anion-stimulated NaCl absorption, ther
eby allowing differential regulation of proximal tubule NaHCO3 and NaC
l transport.