Effect of N-acetylcysteine on sympathetic hyperinnervation in post-infarcted rat hearts

Tsung-Ming Lee, Po Yu Lai, Nen Chung Chang

研究成果: 雜誌貢獻文章同行評審

40 引文 斯高帕斯(Scopus)


AimsThe purpose of this study was to determine whether N-acetylcysteine (NAC) attenuates cardiac sympathetic hyperinnervation through replenishment of glutathione in infarcted rats.Methods and resultsAfter 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 γ-glutamylcysteine ligase.ConclusionChronic 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.
頁(從 - 到)137-146
期刊Cardiovascular Research
出版狀態已發佈 - 1月 2010

ASJC Scopus subject areas

  • 心臟病學與心血管醫學
  • 生理學(醫學)
  • 生理學


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