Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs.
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(omega)-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.
Hajnal
Agnes
A
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P.O. Box 427, H-6701 Hungary.
Nagy
Orsolya
O
Litvai
Agnes
A
Papp
Julius
J
Parratt
James R
JR
Végh
Agnes
A
D000704:Analysis of Variance; D000818:Animals; D004283:Dog Diseases / Q000378:metabolism* / Q000517:prevention & control*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010805:Physical Conditioning, Animal / Q000502:physiology*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000662:veterinary*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control / Q000662:veterinary*; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester