Energy requirement of sodium reabsorption in the thick ascending limb of Henle's loop in the dog kidney: effects of bumetanide and ouabain.

Abstract

To examine whether sodium reabsorption in the thick ascending limb of Henle's loop (TALH) in the dog kidney has a passive component, the ratios between reductions in sodium reabsorption and oxygen consumption (delta Na/delta Qo2 ratio) were measured by inhibiting tubular transport with bumetanide (30 micrograms kg-1) and ouabain (120 ng kg-1 intrarenally). Clearance studies were performed in volume expanded dogs treated with acetazolamide (100 mg kg-1) or maleate (400 mg kg-1). In five acetazolamide-treated dogs, bumetanide gave a delta Na/delta Qo2 ratio of 29.9 +/- 2.5, whereas the combination of bumetanide and ouabain gave 19.0 +/- 0.6. When ouabain was given before bumetanide, ouabain gave a delta Na/delta Qo2 ratio of 19.2 +/- 1.1 and the combination gave 19.9 +/- 1.2. In the maleate-treated dogs, bumetanide gave a delta Na/Qo2 ratio 30.3 +/- 1.7, and the combination of bumetanide and ouabain gave 27.1 +/- 1.5. To localize the metabolic effect of bumetanide and ouabain, local heat production was measured at 18 places in four kidneys with copper-constantan thermocouples. Bumetanide reduced metabolic rate in the outer medulla by 51 +/- 4%, and in the cortex by 16 +/- 6%. Subsequent infusion of ouabain reduced metabolic rate in the outer medulla by only 9 +/- 3%, whereas cortical metabolism was reduced by 33 +/- 4%. The results show that bumetanide mainly acts in the outer medullar where TALH is located, whereas the additional effect of ouabain is mainly located in cortical segment of the nephron including the proximal tubules. Bumetanide inhibits the reabsorption of 30 mol sodium for each mole oxygen consumed, which show that for each 18 mol sodium that are transported through the cells in the TALH in dog kidneys. 12 mol (40%) are transported along the paracellular route without additional requirement of energy.