The role of nitric oxide, reactive oxygen species, and protein kinase C in oxytocin-induced cardioprotection in ischemic rat heart.
Ischemia-reperfusion injury is a common complication of heart disease that is the leading cause of death worldwide. Here, we plan to elucidate oxytocin cardioprotection effects against ischemia-reperfusion via nitric oxide (NO), reactive oxygen species (ROS), and protein kinase C (PKC) in anesthetized rat preconditioned myocardium. Forty-eight Sprague-Dawley rats were equally divided into eight groups. All animals were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin (OT), L-NAME (LNA, a nitric oxide synthase inhibitor), chelerythrine (CHE, a PKC enzyme inhibitor), and N-acetylcysteine (NAC, a ROS scavenger) were used prior to ischemia. Results showed that mean arterial pressure significantly reduced during the first 10 min of ischemia and reperfusion in IR, LNA, CHE, and NAC groups (p<0.05). OT prevented mean arterial pressure decline during early phase of ischemia and reperfusion. Cardioprotective effects of OT in infarct size, plasma levels of creatine kinase-MB and lactate dehydrogenase, severity and incidence of ventricular arrhythmias were abolished by L-NAME, chelerythrine, and N-acetylcysteine (p<0.05). The present study showed that OT pretreatment reduces myocardial infarct size and ventricular arrhythmias, and improves mean arterial pressure via NO production, PKC activation, and ROS balance. These findings provide new insight into therapeutic strategies for ischemic heart disease.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mahdieh
M
Faghihi
Ali Mohammad
AM
Alizadeh
Vahid
V
Khori
Mostafa
M
Latifpour
Saeed
S
Khodayari
D000818:Animals; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology* / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D010121:Oxytocin; D011493:Protein Kinase C