Resistance of mTAL Na+-dependent transporters and collecting duct aquaporins to dehydration in 7-month-old rats.
BACKGROUND
Aging is associated with a defect in urinary concentration in both human and experimental animals. The purpose of these studies was to examine the urinary concentrating ability, the expression of kidney water channels [aquaporins (AQP1 to AQP3)], and medullary thick ascending limb (mTAL) Na+-dependent transporters in old but not senescent versus young animals in response to water deprivation.


METHODS
Two-month-old and 7-month-old rats were placed in metabolic cages and deprived of water for 72 hours. Kidney tissues were isolated and examined for the expression of AQP1 to AQP3 and mTAL, peptide-derived polyclonal antibody specific to kidney apical Na+-K+-2 Cl- cotransporter (BSC1), Na+/H+ exchanger isoform 3 (NHE3), and Na+ pump using semiquantitative immunoblotting and Northern hybridization.


RESULTS
After 72 hours of water deprivation, urine osmolality increased from 1269 to 3830 mOsm/kg H2O in 2-month-old rats, but only from 1027 to 2588 mOsm/kg H2O in 7-month-old rats. In response to water deprivation, AQP2 and AQP3 expression increased significantly in the cortex and medulla of 2-month-old rats but remained unchanged in the medulla or slightly increase in the cortex of 7-month-old animals. AQP1 expression was not altered by dehydration in both groups. The protein abundance of mTAL BSC1, NHE3, and Na+ pump increased significantly in young but remained unchanged in 7-month-old rats subjected to water deprivation.


CONCLUSIONS
Age-related decrease in urinary concentrating ability is an early event, developed before the onset of senescence. This defect results from reduced responsiveness of cortical AQP2 and AQP3 and a blunted response of medullary AQP2 and mTAL BSC1, NHE3, and Na+ pump to dehydration in aging kidneys.
Amlal
Hassane
H
Department of Internal Medicine, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267-0585, USA. Hassane.amlal@uc.edu
Wilke
Catherine
C
D000367:Age Factors; D000818:Animals; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001835:Body Weight; D003681:Dehydration / Q000378:metabolism* / Q000503:physiopathology; D004435:Eating; D007671:Kidney Concentrating Ability / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D014556:Urine; D014868:Water Deprivation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology
C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; C578714:SLC12A1 protein, human; C000613385:SLC9A3 protein, human; C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D051398:Aquaporin 1; D051400:Aquaporin 3; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase