title: Renal expression of sodium transporters and aquaporin-2 in hypothyroid rats.
abstract: Hypothyroidism is associated with significant abnormalities in the renal handling of salt and water. To address the involvement of tubular transport proteins in these abnormalities, rats were rendered pharmacologically hypothyroid and the abundance of major tubular transport proteins was assessed by immunoblot and immunohistochemistry. Hypothyroidism resulted in a marked reduction in kidney size and creatinine clearance along with decreased or unchanged total kidney abundance of the transport proteins. Whereas the proximal tubular type 3 Na/H exchanger (NHE3) and type 2 Na-phosphate cotransporter (NaPi2) stood out by their disproportionately reduced abundance, the bumetanide-sensitive type 2 Na-K-2Cl cotransporter (NKCC2) and aquaporin-2 (AQP2) were unaltered in their total kidney abundance despite a markedly lower kidney mass. The latter proteins in fact showed enhanced immunostaining. Decreased NHE3 and NaPi2 expression was most likely due to a combination of triiodo-l-thyronine (T(3)) deficiency along with a reduced glomerular filtration rate. The increased abundance of NKCC2 and AQP2 may have been caused by an increased action of vasopressin since urinary excretion of this hormone was elevated. On the other hand, the thiazide-sensitive Na-Cl cotransporter; the alpha-, beta-, and gamma-subunits of the amiloride-sensitive epithelial Na channel; and the alpha(1)-subunit of Na-K-ATPase showed a moderate decrease in total kidney abundance that was largely proportional to the smaller kidney mass. Although the observed expression of transporters was associated with a balanced renal sodium handling, altered transporter abundance may become functionally relevant if the hypothyroid kidney is challenged by an additional destabilization of the milieu interieur that has previously been shown to result in an inadequate natriuresis and clinical symptoms.
authors.affiliation: Institut für Anatomie, Charité, Humboldt Universität, 10115 Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitt
authors.forename: Enno
authors.initials: E
authors.lastname: Klussmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Kahl
authors.forename: David H
authors.initials: DH
authors.lastname: Ellison
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D053503:Epithelial Sodium Channels; D007037:Hypothyroidism / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D027981:Symporters / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D013956:Antithyroid Agents; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D002352:Carrier Proteins; D053503:Epithelial Sodium Channels; C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D015222:Sodium Channels; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D027981:Symporters; D014284:Triiodothyronine; D008713:Methimazole; D012964:Sodium; D003404:Creatinine; D000254:Sodium-Potassium-Exchanging ATPase