Effect of N-acetylcysteine on sympathetic hyperinnervation in post-infarcted rat hearts.
OBJECTIVE
The purpose of this study was to determine whether N-acetylcysteine (NAC) attenuates cardiac sympathetic hyperinnervation through replenishment of glutathione in infarcted rats.


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.


CONCLUSIONS
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.
Lee
Tsung-Ming
TM
Department of Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
Lai
Po-Yu
PY
Chang
Nen-Chung
NC
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004452:Echocardiography; D005455:Fluorescent Antibody Technique; D005978:Glutathione / Q000032:analysis / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000032:analysis / Q000235:genetics; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
D019328:Buthionine Sulfoximine; D020932:Nerve Growth Factor; D005978:Glutathione; D000111:Acetylcysteine; D009638:Norepinephrine