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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalCardiovascular Research
Volume85
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Acetylcysteine
Nerve Growth Factor
Glutathione
Vitamins
Infarction
Isoprostanes
Ventricular Remodeling
Tyrosine 3-Monooxygenase
Ligases
Vitamin E
Oxidants
Electric Stimulation
Ascorbic Acid
Ligation
Wistar Rats
Real-Time Polymerase Chain Reaction
Coronary Vessels
Norepinephrine
Down-Regulation
Western Blotting

Keywords

  • Glutathione
  • Myocardial infarction
  • N-acetylcysteine
  • Norepinephrine
  • Sympathetic innervation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Effect of N-acetylcysteine on sympathetic hyperinnervation in post-infarcted rat hearts. / Lee, Tsung-Ming; Lai, Po Yu; Chang, Nen Chung.

In: Cardiovascular Research, Vol. 85, No. 1, 01.2010, p. 137-146.

Research output: Contribution to journalArticle

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