Does the antiarrhythmic effect of ischemic preconditioning in rats involve the L-arginine nitric oxide pathway?
Ischemic preconditioning (PC) has been shown to limit ischemia- and reperfusion-induced arrhythmias. We wished to determine whether the antiarrhythmic effect of PC would be affected by inhibition of the L-arginine nitric oxide (NO) pathway in anesthetized rats. Ischemia and reperfusion were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of PC (three cycles of 2-min coronary artery occlusion and 5-min reperfusion) on development of reperfusion-induced arrhythmias after 5-min coronary artery occlusion was studied in 12 rats. In 24 other rats, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA 10 mg/kg, n = 12) or the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 12), was administered intravenously (i.v.) before PC. In control groups, solvent (n = 15), L-NAME (10 mg/kg i.v., n = 12), L-NMMA (10 mg/kg i.v., n = 12), or L-arginine (L-Arg 100 mg/kg i.v., n = 12) was administered to rats 5 min before coronary artery occlusion without PC. PC significantly reduced the incidence of ventricular premature beats (VPBs) from 100% in the non-PC solvent group to 17%, decreased the incidence of ventricular tachycardia (VT) from 93 to 8%, and abolished the incidence of reversible and irreversible ventricular fibrillation (RVF and IVF: 87 and 47% in the non-PC solvent group, respectively). L-NAME and L-NMMA did not significantly affect the protective effect of PC on reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Cardiovascular and Pulmonary Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Remeysen
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De Clerck
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004562:Electrocardiography / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester