title: Effect of sodium nitrite on ischaemia and reperfusion-induced arrhythmias in anaesthetized dogs: is protein S-nitrosylation involved?
abstract: OBJECTIVE
  To provide evidence for the protective role of inorganic nitrite against acute ischaemia and reperfusion-induced ventricular arrhythmias in a large animal model.
  
  
  METHODS
  Dogs, anaesthetized with chloralose and urethane, were administered intravenously with sodium nitrite (0.2 µmol kg(-1) min(-1)) in two protocols. In protocol 1 nitrite was infused 10 min prior to and during a 25 min occlusion of the left anterior descending (LAD) coronary artery (NaNO2-PO; n = 14), whereas in protocol 2 the infusion was started 10 min prior to reperfusion of the occluded vessel (NaNO2-PR; n = 12). Control dogs (n = 15) were infused with saline and subjected to the same period of ischaemia and reperfusion. Severities of ischaemia and ventricular arrhythmias, as well as changes in plasma nitrate/nitrite (NOx) levels in the coronary sinus blood, were assessed throughout the experiment. Myocardial superoxide and nitrotyrosine (NT) levels were determined during reperfusion. Changes in protein S-nitrosylation (SNO) and S-glutathionylation were also examined.
  
  
  RESULTS
  Compared with controls, sodium nitrite administered either pre-occlusion or pre-reperfusion markedly suppressed the number and severity of ventricular arrhythmias during occlusion and increased survival (0% vs. 50 and 92%) upon reperfusion. There were also significant decreases in superoxide and NT levels in the nitrite treated dogs. Compared with controls, increased SNO was found only in NaNO2-PR dogs, whereas S-glutathionylation occurred primarily in NaNO2-PO dogs.
  
  
  CONCLUSIONS
  Intravenous infusion of nitrite profoundly reduced the severity of ventricular arrhythmias resulting from acute ischaemia and reperfusion in anaesthetized dogs. This effect, among several others, may result from an NO-mediated reduction in oxidative stress, perhaps through protein SNO and/or S-glutathionylation.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Kovács
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Gönczi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Miskolczi
authors.affiliation: Department of Medical Biology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Seprényi
authors.affiliation: Institute of Surgical Research, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kohr
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murphy
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Végh
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D009206:Myocardium / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D011499:Protein Processing, Post-Translational; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D009566:Nitrates; D009573:Nitrites; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D012977:Sodium Nitrite