Cardiovascular Research Advance Access [Accepted Manuscript] published online on December 7, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm092
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction
1 Department of Cardiovascular Medicine, Graduate School of Medical Sciences
2 Department of REDOX Medicinal Science
3 Laboratory of Bio-function Analysis
4 Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, and Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Correspondence: Tomomi Ide, M.D., Ph.D. Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan 812-8582, Tel: +81-92-642-5360, Fax: +81-92-642-5374, e-mail: tomomi_i{at}cardiol.med.kyushu-u.ac.jp
Aims: Redox alteration plays a major role in the pathogenesis of heart failure (HF). Since vagal nerve stimulation (VNS) is known to improve survival and attenuate cardiac remodeling, we hypothesized that VNS may modulate the myocardial redox state.
Methods and Results: Using a chronic HF mouse model, we applied VNS for 15 minutes and measured myocardial redox status using in vivo electron spin resonance (ESR) spectroscopy. Signal decay rate of the nitroxyl probe, an index of redox status, was enhanced in HF compared to sham (0.16 ± 0.01 vs. 0.13 ± 0.01 min–1, P < 0.05; n = 6), and VNS normalized this enhancement (0.13 ± 0.01 min–1, P < 0.05). Atropine sulfate abolished the VNS effects, indicating that the VNS modulates myocardial redox state via muscarinic receptors. N
-Nitro-L-arginine methyl ester (L-NAME) treatment and fixed-rate atrial pacing showed a trend to suppress the VNS effects, suggesting the involvement of NO-based signaling and myocardial oxygen consumption. Moreover, VNS decreased the myocardial norepinephrine level (0.25 ± 0.07 vs. 0.60 ± 0.12 ng/mL, P < 0.05; n = 6). ROS production from cultured cardiomyocytes was enhanced by β-adrenergic activation, which was partially antagonized by 10 µmol/L acetylcholine (ACh) (relative value compared to control: NE 3.7 ± 0.5, NE + ACh 2.5 ± 0.3, P < 0.05; n = 12).
Conclusions: The present study suggests that VNS modulates the cardiac redox status and adrenergic drive, and thereby suppresses free radical generation in the failing heart.
Time for primary review: 13
Related Article
CiteULike 
Connotea 
Del.icio.us What's this?
Cardiovasc Res 2008 77: 609-611.
This article has been cited by other articles:
|
|
 |
|
  C. Vecoli and N. Paolocci When the heart sleeps... Is the vagus resetting the myocardial 'redox clock'? Cardiovasc Res, March 1, 2008; 77(4): 609 - 611. [Full Text] [PDF]
|
|