Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.
Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.
Department of Physiological Science-Federal University of Espirito Santo, Vitória, ES, Brazil.
Rebeca Caldeira Machado
RC
Berger
Department of Physiological Science-Federal University of Espirito Santo, Vitória, ES, Brazil.
Paula Frizera
PF
Vassallo
Heart Institute (InCor) University of São Paulo Medical School, São Paulo, SP, Brazil.
Renato de Oliveira
Rde O
Crajoinas
Department of Physiology and Biophysics -Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Marilene Luzia
ML
Oliveira
Heart Institute (InCor) University of São Paulo Medical School, São Paulo, SP, Brazil.
Flávia Letícia
FL
Martins
Department of Morphology-Federal University of Espirito Santo, Vitória, ES, Brazil.
Breno Valentim
BV
Nogueira
Heart Institute (InCor) University of São Paulo Medical School, São Paulo, SP, Brazil.
Daisy
D
Motta-Santos
Department of Morphology-Federal University of Espirito Santo, Vitória, ES, Brazil.
Isabella Binotti
IB
Araújo
Department of Physiological Science-Federal University of Espirito Santo, Vitória, ES, Brazil.
Ludimila
L
Forechi
Heart Institute (InCor) University of São Paulo Medical School, São Paulo, SP, Brazil.
Adriana Castello Costa
AC
Girardi
Department of Physiology and Biophysics -Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Robson Augusto Souza
RA
Santos
Department of Physiological Science-Federal University of Espirito Santo, Vitória, ES, Brazil.
José Geraldo
JG
Mill
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004039:Diet, Sodium-Restricted; D060730:Glomerular Filtration Barrier / Q000378:metabolism; D006973:Hypertension / Q000178:diet therapy* / Q000473:pathology / Q000652:urine; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System; D017673:Sodium Chloride, Dietary / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D017673:Sodium Chloride, Dietary; C113267:nephrin; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2