title: Potential mechanisms of low-sodium diet-induced cardiac disease: superoxide-NO in the heart.
abstract: BACKGROUND
  Patients on a low salt (LS) diet have increased mortality.
  
  
  OBJECTIVE
  To determine whether reduction in NO bioactivity may contribute to the LS-induced cardiac dysfunction and mortality.
  
  
  RESULTS
  Adult male mongrel dogs were placed on LS (0.05% sodium chloride) for 2 weeks. Body weight (25.4 + or - 0.4 to 23.6 + or - 0.4 kg), left ventricular systolic pressure (137.0 + or - 3.4 to 124.0 + or - 6.7 mm Hg), and mean aortic pressure (111 + or - 3.1 to 98 + or - 4.3 mm Hg) decreased. Plasma angiotensin II concentration increased (4.4 + or - 0.7 to 14.8 + or - 3.7 pg/mL). Veratrine-induced (5 microg/kg) NO-mediated vasodilation was inhibited by 44% in LS; however, the simultaneous intravenous infusion of ascorbic acid or apocynin acutely and completely reversed this inhibition. In LS heart tissues, lucigenin chemiluminescence was increased 2.3-fold to angiotensin II (10(-8) mol/L), and bradykinin (10(-4) mol/L) induced reduction of myocardial oxygen consumption in vitro was decreased (40 + or - 1.3% to 16 + or - 6.3%) and completely restored by coincubation with tiron, tempol or apocynin. Switching of substrate uptake from free fatty acid to glucose by the heart was observed (free fatty acid: 8.97 + or - 1.39 to 4.53 + or - 1.12 micromol/min; glucose: 1.31 + or - 0.52 to 6.86 + or - 1.78 micromol/min). Western blotting indicated an increase in both p47(phox) (121%) and gp91(phox) (44%) as did RNA microarray analysis (433 genes changed) showed an increase in p47(phox) (1.6-fold) and gp91(phox) (2.0 fold) in the LS heart tissue.
  
  
  CONCLUSIONS
  LS diet induces the activation of the renin-angiotensin system, which increases oxidative stress via the NADPH oxidase and attenuates NO bioavailability in the heart.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suematsu
authors.forename: Caroline
authors.initials: C
authors.lastname: Ojaimi
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.forename: Zipping
authors.initials: Z
authors.lastname: Wang
authors.forename: Yester
authors.initials: Y
authors.lastname: Skayian
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Xu
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhang
authors.forename: Pawel M
authors.initials: PM
authors.lastname: Kaminski
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolin
authors.forename: Gabor
authors.initials: G
authors.lastname: Kaley
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hintze
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000627:therapeutic use; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D003331:Coronary Vessels / Q000378:metabolism; D004039:Diet, Sodium-Restricted / Q000009:adverse effects*; D004285:Dogs; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics; D007262:Infusions, Intravenous; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D009569:Nitric Oxide / Q000172:deficiency / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010101:Oxygen Consumption; D012084:Renin-Angiotensin System / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014702:Veratrine / Q000494:pharmacology; D015431:Weight Loss
chemical_list: D000098:Acetophenones; D005227:Fatty Acids; D007773:Lactates; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; C056165:acetovanillone; D019255:NADPH Oxidases; D014702:Veratrine; D005947:Glucose; D001205:Ascorbic Acid