The beneficial effects of peroxynitrite on ischaemia-reperfusion arrhythmias in rat isolated hearts.
The simultaneous production of nitric oxide (NO) and superoxide leads to the formation of a potent toxic metabolite peroxynitrite (ONOO(-)). However, ONOO(-) at low concentrations has been found to exert cardioprotective effects. The purpose of the present study was to investigate the effects of exogenous ONOO(-) on ischaemia-reperfusion arrhythmias. We studied the concentration-response effects of ONOO(-) (0.4, 4, 40 microM ml(-1) min(-1) for 20 min) in rat isolated hearts perfused with Krebs-Henseleit solution. The 0.4 microM concentration of ONOO(-) was selected for further experiments since it did not affect the sinus rhythm. In the hearts subjected to 10 min of ischaemia followed by 10 min of reperfusion during 0.4 microM ml(-1) min(-1) ONOO(-) infusion, the incidence of ventricular fibrillation was decreased significantly from 93% to 38% (n=8) and none of the hearts had an irreversible ventricular fibrillation. Urate, a ONOO(-) scavenger (at 1 mM, n=7), added to the perfusate 5 min prior to the coronary artery occlusion and maintained throughout the experimental period, did not significantly modify the beneficial effects of ONOO(-). Although L-N(G)-nitroarginine methylester (L-NAME) (100 microM, n=8) had no effect, superoxide dismutase (10 U ml(-1))+catalase (100 U ml(-1)) increased the number of ventricular ectopic beats from 91+/-32 to 286+/-83 (n=5) and augmented the incidence of irreversible ventricular fibrillation from 0% to 60%. There were no marked changes in the time of onset of the first arrhythmias in any group. These results suggest that ONOO(-) at a low concentration may exert beneficial effects on ischaemia-reperfusion-induced arrhythmias in rat isolated hearts.
Altug
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Department of Pharmacology, Faculty of Pharmacy, Gazi University, Hipodrom, 06330, Ankara, Turkey. saltug@tr-net.net.tr
Demiryürek
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Cakici
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Kanzik
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D002374:Catalase / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D009566:Nitrates; C039642:peroxynitric acid; D014527:Uric Acid; D002374:Catalase; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester