期刊
CARDIOVASCULAR RESEARCH
卷 85, 期 1, 页码 137-146出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvp286
关键词
Glutathione; Myocardial infarction; N-acetylcysteine; Norepinephrine; Sympathetic innervation
资金
- Chi-Mei Medical Center [CMFHR9744, 98CM-TMU03]
- National Health Research Institutes [NHRI-EX98-9841SI]
- Department of Health, Republic of China [DOH98-TD-I-111-TM001]
Aims The purpose of this study was to determine whether N-acetylcysteine (NAC) attenuates cardiac sympathetic hyper-innervation through replenishment of glutathione in infarcted rats. Methods and results After ligation of the coronary artery, male Wistar rats were randomized to either vehicle, NAC, or vitamins C + E groups for 4 weeks. Post-infarction was associated with increased oxidant release, as measured by tissue isoprostane and myocardial glutathione. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham-operated rats. Sympathetic hyperinnervation was blunted after administering NAC, as assessed by immunofluorescent analysis of tyrosine hydroxylase and western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in the vehicle-treated infarcted rats were significantly higher than those in animals treated with NAC. Although NAC and vitamins showed similar effects on ventricular remodelling, only NAC demonstrated beneficial effects on sympathetic hyperinnervation. Furthermore, the effects of NAC on nerve growth factor were abolished by administering L-buthionine sulfoximinem, an inhibitor of gamma-glutamylcysteine ligase. Conclusion Chronic use of NAC, but not vitamins, after infarction is associated with down-regulation of nerve growth factor proteins, probably through a glutathione-dependent pathway, and thus plays a critical role in the beneficial effect on the arrhythmogenic response to programmed electrical stimulation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据