Is there a role of inducible nitric oxide synthase activation in the delayed antiarrhythmic effect of sodium nitrite?

• Published in: Canadian journal of physiology and pharmacology Vol. 95; no. 4; pp. 447 - 454
• Main Authors: Demeter-Haludka, Vivien, Juhász, László, Kovác, Mária, Gardi, János, Végh, Ágnes
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.04.2017; Canadian Science Publishing NRC Research Press
• Subjects: Animals; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - therapeutic use; Arrhythmia; arrhythmias; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - prevention & control; arythmies; beta-Aminoethyl Isothiourea - pharmacology; Coronary vessels; delayed protection; Dogs; Health aspects; Hemodynamics - drug effects; ischaemia–reperfusion; Ischemia; Ischemic Preconditioning, Myocardial - methods; ischémie–reperfusion; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - etiology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; nitrite de sodium; oxyde nitrique; protection retard; Sodium nitrite; Sodium Nitrite - administration & dosage; Sodium Nitrite - pharmacology; Sodium Nitrite - therapeutic use; Studies; Tachycardia, Ventricular - etiology; Tachycardia, Ventricular - prevention & control; nitrite de sodium; arythmies; nitric oxide; oxyde nitrique; arrhythmias; ischaemia–reperfusion; ischémie–reperfusion; sodium nitrite; delayed protection; protection retard
• DOI: 10.1139/cjpp-2016-0357
• ISSN: 0008-4212

This study aimed to examine whether inducible nitric oxide synthase (iNOS) plays a role in the delayed antiarrhythmic effect of sodium nitrite. Twenty-one dogs were infused intravenously with sodium nitrite (0.2 μmol·kg –1 ·min –1 ) for 20 min, either in the absence (n = 12) or in the presence of the iNOS inhibitor S-(2-aminoethyl)-isothiourea (AEST) (total dose 2.0 mg·kg –1 i.v., n = 9). Control dogs (n = 12) were given saline. Twenty-four hours later, all of the dogs were subjected to a 25 min period occlusion of the left anterior descending coronary artery followed by rapid reperfusion. Dogs treated with AEST and nitrite received again AEST prior to the occlusion. Compared with the controls, sodium nitrite markedly reduced the number of ectopic beats, the number and incidence of ventricular tachycardia, and the incidence of ventricular fibrillation during occlusion and increased survival (0% versus 50%) from the combined ischaemia and reperfusion insult. Although AEST completely inhibited iNOS activity, the nitrite-induced increase in NO bioavailability during occlusion was not substantially modified. Furthermore, AEST attenuated but did not completely abolish the antiarrhythmic effect of nitrite. The marked delayed antiarrhythmic effect of sodium nitrite is not entirely due to the activation of iNOS; other mechanisms may certainly play a role.