Kidney oxygen consumption, carbonic anhydrase, and proton secretion.
Oxygen consumed by the kidney (Q(O(2))) is primarily obligated to sodium reabsorption (T(Na)). The relationship of Q(O(2)) to T(Na) (Q(O(2))/T(Na)) may be altered by hormones and autacoids. To examine whether Q(O(2))/T(Na) depends on the mechanism of sodium reabsorption, we first evaluated the effects on Q(O(2)) and Q(O(2))/T(Na) of benzolamide (BNZ), a proximal diuretic that works by inhibiting membrane carbonic anhydrase. During BNZ infusion in anesthetized rats, Q(O(2)) increased by 50% despite a 25% decline in T(Na). However, BNZ failed to increase Q(O(2))/T(Na) when 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 Q(O(2))to 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 Q(O(2)) and 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.
Deng
Aihua
A
Division of Nephrology-Hypertension, Univ. of California, San Diego and VASDHS, 3350 La Jolla Village Drive (9111-H San Diego, CA 92161, USA.
Miracle
Cynthia M
CM
Lortie
Mark
M
Satriano
Joseph
J
Gabbai
Francis B
FB
Munger
Karen A
KA
Thomson
Scott C
SC
Blantz
Roland C
RC
D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D002256:Carbonic Anhydrases