title: Eplerenone suppresses aldosterone/ salt-induced expression of NOX-4.
abstract: BACKGROUND
  Salt-induced hypertension in the Dahl rat is associated with increases in angiotensin II, aldosterone, free radical generation and endothelial dysfunction. However, little is known about the specific mechanism(s) associated with the end-organ damage effects of aldosterone. We hypothesised that eplerenone reduces kidney damage by blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
  
  
  METHODS
  Dahl salt-sensitive rats fed either a low-salt (LS) or high-salt (HS) diet were treated with aldosterone in the presence of eplerenone or apocynin. Indirect blood pressure was measured prior to start of diet and weekly thereafter. Levels of plasma nitric oxide (NO) and urinary 8-isoprostane were measured following treatment. Protein levels of selected subunits of NADPH were assessed by western blot.
  
  
  RESULTS
  Eplerenone and apocynin inhibited the rise in blood pressure induced by HS and/or aldosterone. This observation was accompanied with a parallel change in kidney protein levels of NADPH oxidase 4 (NOX-4) and p22phox. Aldosterone and high salt were associated with lower NO levels and greater renal oxidative stress.
  
  
  CONCLUSIONS
  NADPH oxidase is associated with the vascular and renal remodelling observed in high dietary salt intake. Aldosterone-induced expression of NOX-4 plays a pivotal role in the end-organ damage effect of aldosterone, as eplerenone tended to reduce kidney damage and inhibit NOX expression.
authors.affiliation: Morehouse School of Medicine, GA 30310-1495, USA. bayorh@msm.edu
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Bayorh
authors.forename: Aisha
authors.initials: A
authors.lastname: Rollins-Hairston
authors.forename: Jeffery
authors.initials: J
authors.lastname: Adiyiah
authors.forename: Deborah
authors.initials: D
authors.lastname: Lyn
authors.forename: Danita
authors.initials: D
authors.lastname: Eatman
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D000077545:Eplerenone; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D021122:Protein Subunits / Q000378:metabolism; D011507:Proteinuria / Q000097:blood / Q000473:pathology; D051381:Rats; D020303:Rats, Inbred Dahl; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013599:Systole / Q000187:drug effects; D016482:Urinalysis
chemical_list: D000098:Acetophenones; D021122:Protein Subunits; D017673:Sodium Chloride, Dietary; C075750:8-epi-prostaglandin F2alpha; D013148:Spironolactone; D009569:Nitric Oxide; D000450:Aldosterone; D000077545:Eplerenone; D012964:Sodium; C056165:acetovanillone; D015237:Dinoprost; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat