Analysis of energy metabolism and mechanism of loop diuretics in the thick ascending limb of Henle's loop in dog kidneys.
OBJECTIVE
The thick ascending limb of Henle's loop (TALH) absorbs up to 40% of filtered NaCl in volume-expanded dogs. To examine if a fraction of this absorption is passive, NaHCO3 absorption and associated NaCl absorption in proximal tubules were inhibited by acetazolamide, a carbonic anhydrase inhibitor.


RESULTS
Ouabain, a specific inhibitor of Na,K-ATPase activity, reduced the remaining NaCl absorption and renal oxygen consumption in a ratio DeltaNa/DeltaO2 = 18, as expected for active transport. However, the responses to two loop diuretics were DeltaNa/DeltaO2 = 24 for ethacrynic acid and DeltaNa/DeltaO2 = 30 for bumetanide. Both loop diuretics induced potassium secretion. By superimposing ouabain potassium secretion was stopped and DeltaNa/DeltaO2 = 18 restored. Replacement of half of the circulating NaCl with Na2SO4 gave stop-flow pattern similar to those obtained after ethacrynic acid.


CONCLUSIONS
Low entry of some sodium ions thorugh the apical membrane is permitted despite low chloride supply or blockade by loop diuretics of chloride entry by the Na-K-2Cl transporter. Continued Na-K-ATPase activity causes secretion of potassium ions through the apical ion channel, ethacrynic acid being more kaliuretic and less natriuretic than bumetanide. Greater paracellular recycling of sodium ions after bumetanide maintains ionic balance. In contrast, under normal conditions excess entry of chloride by the Na-K-2Cl-transporter leads to paracellular back-diffusion of chloride rather than paracellular absorption of sodium ions, consistent with DeltaNa/DeltaO2 = 18 after ouabain. Thus all NaCl transport along TALH is active in vivo, whereas absorption of other cations, such as lithium, probably is passive.
Kiil
F
F
Institute for Experimental Medical Research, University of Oslo, Ullevål University Hospital, Oslo, Norway.
Sejersted
O M
OM
D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D004232:Diuretics / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000502:physiology; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D017693:Sodium Bicarbonate / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*
D002257:Carbonic Anhydrase Inhibitors; D004232:Diuretics; D004791:Enzyme Inhibitors; D012965:Sodium Chloride; D010042:Ouabain; D017693:Sodium Bicarbonate; D012964:Sodium; D000086:Acetazolamide; D011188:Potassium