Effect of metabolic acidosis on nacl transport in the proximal
tubule.
Wang, Tong, Allan L. Egbert, Jr., Peter S. Aronson, and Gerhard
Giebisch.
Departments of Cellular and Molecular Physiology, and Internal
Medicine, Yale University School of Medicine, New Haven, CT 06520
-8026
APStracts 5:0034F, 1998.
In metabolic acidosis, the capacity of the proximal tubule for
bicarbonate absorption is enhanced, whereas NaCl reabsorption is
inhibited. Recent evidence indicates that transcellular NaCl
absorption in the proximal tubule is mediated by apical membrane Cl-
-formate exchange and Cl--oxalate exchange in parallel with recycling
of these organic anions. We evaluated whether the effect of metabolic
acidosis to inhibit NaCl reabsorption in the proximal tubule is due
at least in part to inhibition of organic anion-dependent NaCl
transport in this nephron segment. Absorption rates of bicarbonate
(JHCO3), chloride (JCl) and fluid (Jv) were measured in rat proximal
tubule segments microperfused in situ. We confirmed that metabolic
acidosis stimulates JHCO3 in tubules microperfused with 25 mM HCO3-,
pH 7.4. For measurements of JCl, tubules were microperfused with a
low bicarbonate (5 mM), high chloride solution, simulating conditions
in the late proximal tubule. Under these conditions, baseline JCl and
Jv measured in the absence of formate and oxalate were not
significantly different between control and acidotic rats. However,
whereas addition of 50 [mu]M formate or 1 [mu]M oxalate to luminal
and capillary perfusates markedly stimulated JCl and Jv in control
rats, formate and oxalate failed to stimulate JCl and Jv in acidotic
rats. We conclude that metabolic acidosis markedly down-regulates
organic anion-stimulated NaCl absorption, thereby allowing
differential regulation of proximal tubule NaHCO3 and NaCl transport.
Received 29 July 1997; accepted in final form 5 February 1998.
APS Manuscript Number F253-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998