Aldosterone effects on glomerular structure and function.
OBJECTIVE
Experimental evidence suggests that aldosterone directly contributes to organ damage by promoting cell growth, fibrosis, and inflammation. Based on these premises, this work aimed to assess the glomerular effects of aldosterone, alone and in combination with salt.


METHODS
After undergoing uninephrectomy, 75 rats were allocated to five groups: control, salt diet, aldosterone, aldosterone + salt diet, aldosterone + salt diet and eplerenone, and they were all studied for four weeks. We focused on glomerular structural, functional, and molecular changes, including slit diaphragm components, local renin-angiotensin system activation, as well as pro-oxidative and profibrotic changes.


RESULTS
Aldosterone significantly increased systolic blood pressure, led to glomerular hypertrophy, mesangial expansion, and it significantly increased the glomerular permeability to albumin and the albumin excretion rate, indicating the presence of glomerular damage. These effects were worsened by adding salt to aldosterone, while they were reduced by eplerenone. Aldosterone-induced glomerular damage was associated with glomerular angiotensin-converting enzyme (ACE) 2 downregulation, with ACE/ACE2 ratio increase, ANP decrease, as well as with glomerular pro-oxidative and profibrotic changes.


CONCLUSIONS
Aldosterone damages not only the structure but also the function of the glomerulus. ACE/ACE2 upregulation, ACE2 and ANP downregulation, and pro-oxidative and profibrotic changes are possible mechanisms accounting for aldosterone-induced glomerular injury.
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy stella.bernardi@aots.sanita.fvg.it.
Stella
S
Bernardi
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy Centre for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Switzerland.
Barbara
B
Toffoli
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy.
Cristina
C
Zennaro
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy.
Fleur
F
Bossi
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy.
Pasquale
P
Losurdo
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy.
Andrea
A
Michelli
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy.
Renzo
R
Carretta
Division of Internal Medicine and Hypertension, University of Torino, Italy.
Paolo
P
Mulatero
Department of Medical and Surgical Sciences, University of Padova, Italy.
Francesco
F
Fallo
Division of Internal Medicine and Hypertension, University of Torino, Italy.
Franco
F
Veglio
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Italy.
Bruno
B
Fabris
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D017673:Sodium Chloride, Dietary; D000450:Aldosterone
ACE2; ANP; Aldosterone; fibrosis; glomerular permeability; glomerulus; oxidative stress