Inhibition of transcellular NaCl reabsorption in dog kidneys during hypercalcemia.
Reduced concentrating and diluting capacity of the kidney in acute and chronic hypercalcemia may partly be due to inhibition of transcellular sodium reabsorption (RNa) in the thick ascending limb of Henle's loop. To examine this hypothesis, local heat production and RNa were measured during normo- and hypercalcemia at comparable glomerular filtration rate (GFR) in volume expanded, anesthetized dogs. Changes in proximal RNa which might occur during CaCl2 infusion, were minimized by infusing acetazolamide (75 mg/kg body wt iv). When ultrafiltrable calcium was increased from 1.12 +/- 0.09 to 2.95 +/- 0.10 mmol/l, cortical heat production was unchanged, whereas outer medullary heat production fell by 32 +/- 4%. RNa was reduced by 32 +/- 6%. Bicarbonate reabsorption did not change but calcium reabsorption and potassium excretion increased significantly. The potassium content of cortex and outer medulla increased during hypercalcemia, whereas ouabain, an inhibitor of Na+, K+-ATPase reduces the potassium content. We conclude that hypercalcemia does not inhibit transcellular RNa in the diluting segment by a direct effect on the Na+, K+-ATPase or the mitochondria, but by interfering with the coupled NaCl transport across the luminal cell membrane.
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D004285:Dogs; D004976:Ethacrynic Acid / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate; D006934:Hypercalcemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001639:Bicarbonates; D012965:Sodium Chloride; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002122:Calcium Chloride; D004976:Ethacrynic Acid; D011188:Potassium