Role of Muscarinic Acetylcholine Receptors in Oxytocin-Induced Cardioprotection Against Ischemia-Reperfusion Injury in Rats.

Abstract

Oxytocin (OT) has been shown to provide myocardial protection against ischemia-reperfusion (I/R) injury. This study investigates the involvement of muscarinic receptors in the OT-induced cardioprotection, focusing on its potential mechanisms and effects on myocardial infarction (MI) and ischemic arrhythmias. Male rats anesthetized with pentobarbital sodium were subjected to 25-min ischemia followed by 120-min reperfusion after intraperitoneal administration of OT (0.01 μg), atropine (1.5 µg/kg), or saline. Cardioprotection was evaluated by monitoring lactate dehydrogenase (LDH), malondialdehyde (MDA), and cardiac creatine kinase isoenzyme (CK-MB) levels, infarct size, arrhythmia severity, ventricular fibrillation, and mortality. OT markedly reduced infarct size, oxidative stress, and the severity of ischemic arrhythmias, including ventricular tachycardia and ventricular fibrillation, compared with saline-treated I/R animals. OT also significantly improved survival rates. Pretreatment with atropine abolished most protective effects of OT but did not significantly alter its suppression of ventricular fibrillation, suggesting the involvement of muscarinic receptor-independent mechanisms. These findings highlight that the OT-induced cardioprotection, mediated in part by acetylcholine (ACh) locally released in the left ventricle, extends beyond infarct limitation to include potent anti-arrhythmic effects. The dual impact of OT on MI and arrhythmias provides insights into the mechanisms underlying its preconditioning effect and its potential application in MI management.