Is preconditioning by oxytocin administration mediated by iNOS and/or mitochondrial KATP channel activation in the in vivo anesthetized rabbit heart?

Aims: Oxytocin (OXT) pretreatment protects the heart during ischemia-reperfusion injury by activating ATP-dependent potassium (K-ATP) channels. The aim of the current study was to elucidate the roles of nitric oxide synthaseNOS and myocardial biochemistry in the cardioprotective effects of OXT and ischemic preconditioning (IPC). Main methods: Male New Zealand White anesthetized rabbits (13 groups) were subjected to 30 min of occlusion of the left coronary artery and 120 min of reperfusion with or without IPC. Key findings: IK (1 cycle), OXT (0.03 mu g/kg, i.p.) or IPC + OXT yield significant infarct size reductions (21.8 +/- 1.5%, 20.5 +/- 12% and 19.4 +/- 1.4%, respectively, versus 38.9 +/- 3.5% in the S-CONT group; P<0.01) and antiarrhythmic effects, including VF (0%, 0% and 0%, versus 50% in S-CONT group; P<0.05) sustained VT (13%, 13% and 13%, versus 100% in S-CONT group; P<0.005) and other arrhythmias (25%, 13% and 25%, versus 100% in S-CONT group; P<0.005, P<0.01 and P<0.005, respectively). Atosiban (ATO, a selective OXT receptor antagonist), 5-HD and L-NAME (a nonspecific NOS inhibitor) abolished the beneficial effects of IPC and OXT, suggesting that the benefits are achieved via selective activation of OXT receptors, mitochondrial K-ATP channels and NO. An iNOS inhibitor (1400 W) blocked the beneficial effects of IPC but not OXT. The IPC, OXT, IPC + OXT and 1400 W + OXT interventions significantly preserved ATP levels in the heart. Significance: This study demonstrates similarities between acute OXT pretreatment and IPC in terms of infarct size reduction, antiarrhythmic activity, and metabolic status. (C) 2012 Elsevier Inc. All rights reserved.