The role of nitric oxide, superoxide and peroxynitrite in the anti-arrhythmic effects of preconditioning and peroxynitrite infusion in anaesthetized dogs.
OBJECTIVE
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.


METHODS
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.


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
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.
Kiss
Attila
A
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Medical Center, Szeged, Hungary.
Juhász
László
L
Seprényi
György
G
Kupai
Krisztina
K
Kaszaki
József
J
Végh
Agnes
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D007261:Infusions, Intra-Arterial; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000008:administration & dosage* / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D026361:Reactive Nitrogen Species; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine