title: Modulation of gap junctions by nitric oxide contributes to the anti-arrhythmic effect of sodium nitroprusside?
abstract: OBJECTIVE
  Nitric oxide (NO) donors provide a preconditioning-like anti-arrhythmic protection in the anaesthetized dog. As NO may modulate gap junction (GJ) function, the present study investigated whether this anti-arrhythmic effect is due to a modification of GJs by NO, derived from the NO donor sodium nitroprusside (SNP).
  
  
  METHODS
  In chloralose-urethane-anaesthetized, open-chest dogs, either saline (controls; n= 11) or SNP (0.2 microg x kg(-1) x min(-1); n= 10) was infused at a rate of 0.5 mL x min(-1) by the intracoronary route. The infusions were started 20 min prior to and maintained throughout the entire 60 min occlusion period of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, tissue electrical impedance and permeability, as well as the phosphorylation of connexin43, were assessed.
  
  
  RESULTS
  Compared with the controls, SNP infusion markedly suppressed the total number of ventricular premature beats (666 +/- 202 vs. 49 +/- 18; P < 0.05), and the number of ventricular tachycardiac episodes (8.1 +/- 2.3 vs. 0.2 +/- 0.1; P < 0.05) without significantly modifying the incidence of ventricular tachycardia or ventricular fibrillation. The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) and tissue electrical impedance changes were significantly less in the SNP-treated dogs. SNP improved GJ permeability and preserved the phosphorylated form of connexin43.
  
  
  CONCLUSIONS
  The anti-arrhythmic protection resulting from SNP infusion in the anaesthethized dog may, in part, be associated with the modulation of gap junctional function by NO.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Szeged, Hungary. vegh@phcol.szote.u-szeged.hu
authors.forename: Márton
authors.initials: M
authors.lastname: Gönczi
authors.forename: Rita
authors.initials: R
authors.lastname: Papp
authors.forename: Mária
authors.initials: M
authors.lastname: Kovács
authors.forename: György
authors.initials: G
authors.lastname: Seprényi
authors.forename: Agnes
authors.initials: A
authors.lastname: Végh
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018031:Connexin 43 / Q000378:metabolism; D023921:Coronary Stenosis / Q000150:complications; D003331:Coronary Vessels; D004285:Dogs; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018879:Ventricular Premature Complexes / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide