Kidney oxygen consumption, carbonic anhydrase, and proton secretion

Abstract

Oxygen consumed by the kidney (QO2) is primarily obligated to sodium reabsorption (TNa). The relationship of QO2to TNa(QO2/TNa) may be altered by hormones and autacoids. To examine whether QO2/TNadepends on the mechanism of sodium reabsorption, we first evaluated the effects on QO2and QO2/TNaof benzolamide (BNZ), a proximal diuretic that works by inhibiting membrane carbonic anhydrase. During BNZ infusion in anesthetized rats, QO2increased by 50% despite a 25% decline in TNa. However, BNZ failed to increase QO2/TNawhen given along with the adenosine A1 receptor blocker, DPCPX, which inhibits basolateral Na-bicarbonate cotransport (NBC1), or EIPA, which inhibits sodium-hydrogen exchange (NHE). Incubating freshly harvested rat proximal tubules with BNZ also caused QO2to increase by 62%, an effect that was prevented by blocking the apical NHE3 with S3226. Blocking NBC1 or NHE3 in the proximal tubule will have opposite effects on cell pH, but both maneuvers should reduce active chloride transport. In conclusion, inhibiting membrane carbonic anhydrase in the proximal tubule increases QO2and reduces the energy efficiency of sodium reabsorption by the kidney. This is not purely due to shifting the burden of reabsorption to a more expensive site downstream from the proximal tubule. Instead, increased cost may be incurred within the proximal tubule as the result of increased active chloride transport.