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

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-minute ischemia followed by 120-minute reperfusion after intraperitoneal administration of OT (0.01 μg), atropine (1.5 µg/kg), or saline. Cardioprotection was evaluated by monitoring lactate dehydrogenase, malondialdehyde, and cardiac creatine kinase isoenzyme levels, infarct size, arrhythmia severity, ventricular fibrillation (VF), and mortality. OT markedly reduced infarct size, oxidative stress, and the severity of ischemic arrhythmias, including ventricular tachycardia and VF, 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 VF, suggesting the involvement of muscarinic receptor-independent mechanisms. These findings highlight that the OT-induced cardioprotection, mediated in part by acetylcholine locally released in the left ventricle, extends beyond infarct limitation to include potent antiarrhythmic 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.