Protection against Ischemia-Induced Oxidative Stress Conferred by Vagal Stimulation in the Rat Heart: Involvement of the AMPK-PKC Pathway

Abstract

Reactive oxygen species (ROS) production is an important mechanism in myocardial ischemia and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of major sources of ROS in the heart. Previous studies showed that vagus nerve stimulation (VNS) is beneficial in treating ischemic heart diseases. However, the effect of VNS on ROS production remains elusive. In this study, we investigated the role of VNS onischemia-induced ROS production. Our results demonstrated that VNS alleviated the myocardial injury, attenuated the cardiac dysfunction, reserved the antioxidant enzyme activity and inhibited the formation of ROS as evidenced by the decreased NADPH oxidase (Nox) activity and superoxide fluorescence intensity as well as the expression of p67phox, Rac1 and nitrotyrosine. Furthermore, VNS resulted in the phosphorylation and activation of adenosine monophosphate activated protein kinase (AMPK), which in turn led to an inactivation of Nox by protein kinase C (PKC); however, the phenomena were repressed by the administration of a muscarinic antagonist atropine. Taken together, these data indicate that VNS decreases ROS via AMPK-PKC-Nox pathway; this may have potential importance for the treatment of ischemic heart diseases.

Acetylcholine Promotes ROS Detoxification Against Hypoxia/reoxygenation-Induced Oxidative Stress Through FoxO3a/PGC-1a Dependent Superoxide Dismutase

“…Our results have indicated that ACh have a protective role in resistance to H/R-induced oxidative stress through the regulation of antioxidant gene SOD. Such a finding is in agreement with our recent study, showing that VNS enhanced the expressions of SOD1 and SOD2 in rat myocardium after myocardial infarction [28]. In addition to SOD, other antioxidants like catalase and glutathione reductase, also play important roles in ROS scavenging.…”

Muscarinic Stimulation Facilitates Sarcoplasmic Reticulum Ca Release by Modulating Ryanodine Receptor 2 Phosphorylation Through Protein Kinase G and Ca/Calmodulin-Dependent Protein Kinase II

“…Based on previous reports, the reduction of ROS during cholinergic modulation could be a result of increased reducing-enzyme(s) activity or inhibition of ROS generation through NADPH oxidase, xanthine oxidase and mitochondria. 65–67 …”

Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A

“…Ekici et al (23) demonstrated that VS exhibits antioxidant efficacy in the treatment of focal cerebral I/R; therefore VS may be capable of suppressing the generation of reactive oxygen species (ROS) in ischemic heart diseases (24,25). VS may also exert its antioxidant effects by suppressing the prolonged opening of the permeable transition pore which promotes the production of ROS (16).…”