Modulation of gap junctions by nitric oxide contributes to the anti-arrhythmic effect of sodium nitroprusside?

Márton Gönczi, Rita Papp, Mária Kovács, György Seprényi, Ágnes Végh

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background and purpose: 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). Experimental approach: In chloralose-urethane-anaesthetized, open-chest dogs, either saline (controls; n = 11) or SNP (0.2 μg·kg -1·min -1; n = 10) was infused at a rate of 0.5 mL·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. Key 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. Conclusion and implications: 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.

Original languageEnglish
Pages (from-to)786-793
Number of pages8
JournalBritish journal of pharmacology
Volume156
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

    Fingerprint

Keywords

  • Arrhythmias
  • Gap junction
  • Myocardial ischaemia
  • NO donors
  • Sodium nitroprusside

ASJC Scopus subject areas

  • Pharmacology

Cite this