AJP - Renal Physiology, Vol 250, Issue 3 476-F482, Copyright © 1986 by American Physiological Society
Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis
N. Bank, H. S. Aynedjian and B. F. Mutz
Microperfusion studies were carried out in rats to examine the abnormality
in proximal tubule HCO3- transport caused by maleic acid administration.
Permeability of the proximal tubule to HCO-3 was measured by perfusing
proximal tubules with a HCO3- -free low-buffer isotonic equilibrium
solution containing acetazolamide after plasma [HCO3-] had been raised by
intravenous NaHCO3 infusion. Insulin recovery in the collected perfusate
was approximately 100% in control and maleic acid-treated rats. CO2 influx
measured by microcalorimetry was not significantly different in control vs.
maleic acid-treated rats. Thus maleic acid did not cause increased
permeability of the proximal tubule to either inulin or HCO3-. In a second
group of experiments, proximal tubule fluid and HCO3- efflux were measured
in paired-reperfusion experiments before and after maleic acid
administration. The perfusion fluid contained 25 mM HCO3- and 120 mM Cl-.
HCO3- absorption was inhibited 25% (79 pmol/min), Na+ was inhibited 22%
(164 pmol/min), and Cl- absorption (calculated as the anion gap) by 85
pmol/min. [HCO3-] in the collected perfusate rose significantly after
maleic acid, presumably accompanied by a fall in [Cl-]. The observations
indicate that proximal renal tubular acidosis (RTA) induced by maleic acid
is characterized by impaired lumen-to-blood transport of sodium bicarbonate
and chloride but not by increased backflux. Based on previously
demonstrated effects of maleic acid on mitochondrial energy metabolism and
cellular ATP levels, we postulate that the principal transport abnormality
is impaired basolateral membrane active sodium transport, leading to a
secondary reduction in brush border Na+-H+ exchange.(ABSTRACT TRUNCATED AT
250 WORDS)
