Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis.
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)
D000141:Acidosis, Renal Tubular / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008298:Maleates; D010477:Perfusion / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D008298:Maleates; C030272:maleic acid