Hassane Amlal1, Catherine Wilke. 1. Department of Internal Medicine, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267-0585, USA. Hassane.amlal@uc.edu
Abstract
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. CONCLUSION: 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.
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 mTALBSC1, NHE3, and Na+ pump increased significantly in young but remained unchanged in 7-month-old rats subjected to water deprivation. CONCLUSION: 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 mTALBSC1, NHE3, and Na+ pump to dehydration in aging kidneys.
Authors: Ingrid F Dos Santos; Sulaiman Sheriff; Sihame Amlal; Rafeeq P H Ahmed; Charuhas V Thakar; Hassane Amlal Journal: Am J Physiol Renal Physiol Date: 2019-01-09