Effect of maleate on tubular protein reabsorption in dog kidneys.
To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg.kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 +/- 3 to 48 +/- 6 mumol.min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the 'trapped-label' method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg.min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg.kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg.min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-beta-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.
Hysing
J
J
Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Norway.
Ostensen
J
J
Tolleshaug
H
H
Kiil
F
F
D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004357:Drug Synergism; D007684:Kidney Tubules / Q000378:metabolism*; D008298:Maleates / Q000494:pharmacology*; D011506:Proteins / Q000493:pharmacokinetics*
D008298:Maleates; D011506:Proteins; C030272:maleic acid; D000086:Acetazolamide