Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs

• Published in: Life sciences (1973) 2005-09, Vol.77 (16), p.1960-1971
• Main Authors: Hajnal, Ágnes, Nagy, Orsolya, Litvai, Ágnes, Papp, Julius, Parratt, James R., Végh, Ágnes
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; beta-Aminoethyl Isothiourea - pharmacology; Delayed preconditioning; Dog Diseases - metabolism; Dog Diseases - prevention & control; Dogs; Exercise; Hemodynamics - drug effects; iNOS; Ischaemia-reperfusion; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type II; Physical Conditioning, Animal - physiology; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - veterinary; Ventricular arrhythmias; Ventricular Fibrillation - etiology; Ventricular Fibrillation - metabolism; Ventricular Fibrillation - prevention & control; Ventricular Fibrillation - veterinary
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.02.015

We have shown previously that a single period of treadmill exercise in dogs protects the heart against the severe ventricular arrhythmias that arise when a major (anterior descending) branch of the left coronary artery is occluded following anaesthesia 24 h later. This protection is aminoguanidine sensitive, suggesting a role for nitric oxide (NO) in this exercise-induced delayed antiarrhythmic effect. The present study has further examined the possible role of NO as a mediator and/or as a trigger using the selective induced (iNOS) inhibitor S-(2-aminoethyl)-methyl-isothiourea (AEST) and the specific but not selective nitric oxide synthase inhibitor N ω-nitro-L-arginine-methyl-ester (L-NAME). Exercise markedly reduced the severity of ischaemia and reperfusion-induced ventricular arrhythmias 24 h later. Thus, only one of the dogs (8%) so exercised fibrillated on occlusion (contrast 46% in the control, non-exercised dogs; P < 0.05) and the marked changes in the inhomogeneity of electrical activation that occur in the ischaemic region following occlusion were much reduced ( P < 0.05 compared to controls). This delayed exercise-induced cardioprotection was significantly attenuated by the nitric oxide synthase (NOS) inhibitors L-NAME, given prior to the exercise protocol and by AEST given prior to the coronary artery occlusion. For example, survival from the ischaemia-reperfusion insult was 54% in the exercise dogs, 0% in the controls and 14% in those dogs given a NOS inhibitor. We conclude that nitric oxide (NO) is both the trigger and the mediator of this delayed protection against ischaemia and reperfusion-induced arrhythmias.