Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure.
Heart failure (HF) is associated with a reduced effective circulating volume that drives sodium and water retention and extracellular volume expansion. We therefore hypothesized that Na(+)/H(+) exchanger isoform 3 (NHE3), the major apical transcellular pathway for sodium reabsorption in the proximal tubule, is upregulated in an experimental model of HF. HF was induced in male rats by left ventricle radiofrequency ablation. Sham-operated rats (sham) were used as controls. At 6 wk after surgery, HF rats exhibited cardiac dysfunction with a dramatic increase in left ventricular end-diastolic pressure. By means of stationary in vivo microperfusion and pH-dependent sodium uptake, we demonstrated that NHE3 transport activity was significantly higher in the proximal tubule of HF compared with sham rats. Increased NHE3 activity was paralleled by increased renal cortical NHE3 expression at both protein and mRNA levels. In addition, the baseline PKA-dependent NHE3 phosphorylation at serine 552 was reduced in renal cortical membranes of rats with HF. Collectively, these results suggest that NHE3 is upregulated in the proximal tubule of HF rats by transcriptional, translational, and posttranslational mechanisms. Enhanced NHE3-mediated sodium reabsorption in the proximal tubule may contribute to extracellular volume expansion and edema, the hallmark feature of HF. Moreover, our study emphasizes the importance of undertaking a cardiorenal approach to contain progression of cardiac disease.
Heart Institute, University of São Paulo Medical School, Brazil.
Bruna H
BH
Inoue
Leonardo
L
dos Santos
Thaissa D
TD
Pessoa
Ednei L
EL
Antonio
Bruna P M
BP
Pacheco
Fernanda A
FA
Savignano
Luciene R
LR
Carraro-Lacroix
Paulo J F
PJ
Tucci
Gerhard
G
Malnic
Adriana C C
AC
Girardi
D000818:Animals; D001692:Biological Transport; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D012333:RNA, Messenger; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D017868:Cyclic AMP-Dependent Protein Kinases