title: Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule.
abstract: The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either hypercapnia and hypoxia [8% CO(2) and 13% O(2) (hypercapnic, n = 6) or normal air (controls, n = 6)] in an environmental chamber for 10 days and were killed under the same atmosphere. In hypercapnic rats, arterial pH was lower than controls (7.31 +/- 0.01 vs. 7.39 +/- 0.01, P = 0.03), blood HCO(3)(-) concentration was increased (42 +/- 0.9 vs. 32 +/- 0.24 mM, P < 0.001), arterial Pco(2) was increased (10.76 +/- 0.4 vs. 7.20 +/- 0.4 kPa, P < 0.001), and plasma chloride concentration was decreased (92.2 +/- 0.7 vs. 97.2 +/- 0.5 mM, P < 0.001). Plasma aldosterone levels were unchanged. In the proximal tubule, immunoblotting showed an increased expression of sodium/bicarbonate exchanger protein (188 +/- 22 vs. 100 +/- 11%, P = 0.005), confirmed by immunohistochemistry. Total Na/H exchanger protein expression in the cortex was unchanged by immunoblotting (119 +/- 10 vs. 100 +/- 11%, P = 0.27) and immunohistochemistry. In the cortex, the abundance of pendrin was decreased (51 +/- 9 vs. 100 +/- 7%, P = 0.003) by immunoblotting. Immunohistochemistry revealed that this decrease was clear in both cortical collecting ducts (CCDs) and connecting tubules (CNTs). This demonstrates that pendrin expression can be regulated in acidotic animals with no changes in aldosterone levels and no external chloride load. This reduction of pendrin expression may help in redirecting the CNT and CCD toward chloride excretion and bicarbonate reabsorption, contributing to the increased plasma bicarbonate and decreased plasma chloride of chronic respiratory acidosis.
authors.affiliation: The Water and Salt Research Center, Institute of Anatomy, Bldg. 1234, Univ. of Aarhus, DK-8000 Aarhus C, Denmark.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Seigneux
authors.forename: Hans
authors.initials: H
authors.lastname: Malte
authors.forename: Henrik
authors.initials: H
authors.lastname: Dimke
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Frische
mesh_terms: D000142:Acidosis, Respiratory / Q000503:physiopathology*; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D064026:Calbindins; D002245:Carbon Dioxide / Q000097:blood; D027963:Chloride-Bicarbonate Antiporters / Q000096:biosynthesis*; D002712:Chlorides / Q000097:blood; D015536:Down-Regulation; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000503:physiopathology* / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000076988:Sulfate Transporters; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D064026:Calbindins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D053503:Epithelial Sodium Channels; D064030:S100 Calcium Binding Protein G; C494615:Slc26A4 protein, rat; C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000076988:Sulfate Transporters; D002245:Carbon Dioxide; D025262:Vacuolar Proton-Translocating ATPases; D010100:Oxygen