title: Role of the loop segment in the urinary concentrating defect of hypercalcemia.
abstract: Hypercalcemia is associated with impaired urinary concentrating ability. To explore the mechanism(s) by which hypercalcemia impairs chloride transport in the loop of Henle, we carried out in vivo microperfusion of the loop segment in Sprague-Dawley rats rendered acutely hypercalcemic (12.1 +/- 0.1 mg/dliter) by calcium gluconate infusion. Control rats were infused with sodium gluconate and had normal plasma calcium (8.0 +/- 0.2 mg/dliter). Compared to control, fractional chloride reabsorption was decreased (61 +/- 4 to 50 +/- 3%; P less than 0.05) and early distal chloride increased 74 +/- 6 to 98 +/- 3 mEq/liter (P less than 0.001) in hypercalcemia. During hypercalcemia, infusion of verapamil failed to increase fractional chloride reabsorption (49 +/- 4%; P less than 0.05) or decrease early distal chloride (95 +/- 2; P less than 0.05) toward control values. Similarly, indomethacin did not improve fractional chloride reabsorption (48 +/- 4%; P less than 0.05) or distal chloride concentration (93 +/- 7; P less than 0.05). In control rats infused with Ringers HCO3, the addition of calcium 8.0 mEq/liter to the perfusate increased early distal calcium (9.22 to 3.11 mEq/liter) but was associated with no change in fractional chloride reabsorption (-6 +/- 6%) and a slight decrease in early distal chloride (-9 +/- 3 mEq/liter; P less than 0.05). These data are consistent with the hypothesis that an elevated plasma, not luminal calcium, concentration impairs chloride reabsorption in the loop segment, primarily the ADH-stimulated component. This may have an important role in the urinary concentrating defect of hypercalcemia.
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002125:Calcium Gluconate / Q000633:toxicity; D002712:Chlorides / Q000378:metabolism*; D004872:Ergocalciferols / Q000633:toxicity; D006934:Hypercalcemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007213:Indomethacin / Q000627:therapeutic use; D007671:Kidney Concentrating Ability; D007684:Kidney Tubules / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D002712:Chlorides; D004872:Ergocalciferols; D014700:Verapamil; D002125:Calcium Gluconate; D002118:Calcium; D007213:Indomethacin