Document Detail


The role of nitric oxide, superoxide and peroxynitrite in the anti-arrhythmic effects of preconditioning and peroxynitrite infusion in anaesthetized dogs.
MedLine Citation:
PMID:  20590618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Both ischaemia preconditioning (PC) and the intracoronary infusion of peroxynitrite (PN) suppress ischaemia and reperfusion (I/R)-induced arrhythmias and the generation of nitrotyrosine (NT, a marker of PN). However, it is still unclear whether this latter effect is due to a reduction in nitric oxide (NO) or superoxide (O(2)(-)) production.
EXPERIMENTAL APPROACH: Dogs anaesthetized with chloralose and urethane were infused, twice for 5 min, with either saline (control) or 100 nM PN, or subjected to similar periods of occlusion (PC), 5 min prior to a 25 min occlusion and reperfusion of the left anterior descending coronary artery. Severities of ischaemia and ventricular arrhythmias, as well as changes in the coronary sinus nitrate/nitrite (NOx) levels were assessed throughout the experiment. The production of myocardial NOx, O(2)(-) and NT was determined following reperfusion.
KEY RESULTS: Both PC and PN markedly suppressed the I/R-induced ventricular arrhythmias, compared to the controls, and increased NOx levels during coronary artery occlusion. Reperfusion induced almost the same increases in NOx levels in all groups, but superoxide production and, consequently, the generation of NT were significantly less in PC- and PN-treated dogs than in controls.
CONCLUSIONS AND IMPLICATIONS: Since both PC and the administration of PN enhanced NOx levels during I/R, the attenuation of endogenous PN formation in these dogs is primarily due to a reduction in the amount of O(2) produced. Thus, the anti-arrhythmic effect of PC and PN can almost certainly be attributed to the preservation of NO availability during myocardial ischaemia.
Authors:
Attila Kiss; László Juhász; György Seprényi; Krisztina Kupai; József Kaszaki; Agnes Végh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  160     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-01     Completed Date:  2010-10-07     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1263-72     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Medical Center, Szeged, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / administration & dosage*,  pharmacology
Arrhythmias, Cardiac / drug therapy*,  physiopathology*
Dogs
Female
Infusions, Intra-Arterial
Ischemic Preconditioning, Myocardial / methods*
Male
Nitric Oxide / metabolism*
Peroxynitrous Acid / administration & dosage*,  pharmacology
Reactive Nitrogen Species / metabolism
Superoxides / metabolism*
Tyrosine / analogs & derivatives,  metabolism
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Reactive Nitrogen Species; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 14691-52-2/Peroxynitrous Acid; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine
Comments/Corrections

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