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Am J Physiol Renal Physiol 284: F1056-F1065, 2003. First published January 28, 2003; doi:10.1152/ajprenal.00317.2002
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Vol. 284, Issue 5, F1056-F1065, May 2003

Chronic renal injury-induced hypertension alters renal NHE3 distribution and abundance

Li E. Yang1, Huiqin Zhong2, Patrick K. K. Leong1, Anjana Perianayagam1, Vito M. Campese2, and Alicia A. McDonough1

1 Department of Physiology and Biophysics and 2 Division of Nephrology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9142

Renal cortical phenol injection provokes acute sympathetic nervous system-dependent hypertension and a shift of proximal tubule Na+/H+ exchanger isoform 3 (NHE3) and Na+-Pi cotransporter type 2 (NaPi2) to apical microvilli. This study aimed to determine whether proximal tubule (PT) Na+ transporter redistribution persists chronically and whether the pool sizes of renal Na+ transporters are altered. At 5 wk after a 50-µl 10% phenol injection, blood pressure is elevated: 154 ± 8 vs. 113 ± 11 mmHg after saline injection. Cortical membranes were fractionated into three "windows" enriched in apical brush border (WI), mixed apical and intermicrovillar cleft (WII), and intracellular membranes (WIII). NHE3 relative distribution in these windows, assessed by immunoblots and expressed as %total, remained shifted to apical from intracellular membranes (WI: 25.3 ± 3 in phenol vs.12.7 ± 3% in saline and WIII: 9.1 ± 1.3 in phenol vs. 18.9 ± 3% in saline). NaPi2 and dipeptidyl-peptidase IV also remained shifted to WI, and alkaline phosphatase activity increased 100.9 ± 29.7 (WI) and 51.4 ± 17.5% (WII) in phenol-injected membranes. Na+ transporter total abundance [NHE3, NaPi2, thiazide-sensitive Na-Cl cotransporter, bumetanide-sensitive Na-K-2Cl cotransporter, Na-K-ATPase alpha 1- and beta 1-subunits, and epithelial Na+ channel (ENaC) alpha - and beta -subunits] was profiled by immunoblotting. Only cortical NHE3 abundance was altered, decreasing to 0.56 ± 0.06. The results demonstrate that phenol injury provokes a persistant shift of PT NHE3 and NaPi2 to the apical microvilli, along with a 44% decrease in total NHE3, evidence for an escape mechanism that would counteract the redistribution of a larger fraction of NHE3 to the apical surface by normalizing the total amount of NHE3 in apical membranes.

sodium transport; membrane traffic; sympathetic nervous system; phenol


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