Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure

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art_INOUE_Increased_NHE3_abundance_and_transport_activity_in_renal_2012.PDF (1 MB)
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49
Tipo de produção
article
Data de publicação
2012
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER PHYSIOLOGICAL SOC
Autores
SANTOS, Leonardo dos
PESSOA, Thaissa D.
ANTONIO, Ednei L.
SAVIGNANO, Fernanda A.
CARRARO-LACROIX, Luciene R.
TUCCI, Paulo J. F.
MALNIC, Gerhard
Citação
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v.302, n.1, p.R166-R174, 2012
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Inoue BH, dos Santos L, Pessoa TD, Antonio EL, Pacheco BPM, Savignano FA, Carraro-Lacroix LR, Tucci PJF, Malnic G, Girardi ACC. Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 302: R166-R174, 2012. First published October 26, 2011; doi:10.1152/ajpregu.00127.2011.-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.
Palavras-chave
myocardial injury, renal function, volume homeostasis, radiofrequency ablation
URI
https://observatorio.fm.usp.br/handle/OPI/1448
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Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13