title: Tumour necrosis factor-α and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats.
abstract: 1. Acute myocardial infarction (AMI) often activates the sympathetic system and inhibits the vagal system. Long-term vagal nerve stimulation (VNS) exerts several beneficial effects on the ischaemic heart, including an anti-inflammatory effect. The aim of the present study was to investigate whether short-term VNS during AMI could inhibit tumour necrosis factor (TNF)-α expression and the effect of TNF receptor (TNFR), key components in inflammatory responses to AMI, in a rodent model. 2. Adult male Sprague-Dawley rats were divided into four groups, namely a control (C), VNS (S), AMI (M) and an AMI group subjected to prior VNS (MS). In the S and MS groups, the right vagus nerve was stimulated electrically for 4 h; in the M and MS groups, AMI was induced by occlusion of the left anterior descending coronary artery. Haemodynamic data were monitored continuously using a multichannel physiological recorder. Lactate dehydrogenase (LDH) leakage, creatine kinase (CK) leakage and infarct size were determined. The expression of TNF-α and its receptors were analysed by reverse transcription-polymerase chain reaction, western blotting and ELISA. 3. Compared with the control group, rats in the M group had low blood pressure, high left ventricular (LV) end-diastolic pressure, a depressed maximum dP/dt of LV pressure, higher LDH and CK leakage, a larger infarct size, increased TNF-α levels and an increased TNFR1/TNFR2 ratio. However, these presumably harmful effects of AMI were all significantly ameliorated by VNS during AMI (MS group). 4. In conclusion, VNS can rectify ischaemia-induced cardiac dysfunction partly via inhibition of a TNF-α-mediated signalling pathway.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University, College of Medicine, Xi'an, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Kong
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Tyzh-Chang
authors.initials: TC
authors.lastname: Hwang
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055536:Vagus Nerve Stimulation; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase