Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction.
OBJECTIVE
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 remodelling, we hypothesized that VNS may modulate the myocardial redox state.


RESULTS
Using a chronic HF mouse model, we applied VNS for 15 min and measured myocardial redox status using in vivo electron spin resonance spectroscopy. Signal decay rate of the nitroxyl probe, an index of redox status, was enhanced in HF compared with 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 sulphate abolished the VNS effects, indicating that the VNS modulates myocardial redox state via muscarinic receptors. N(omega)-Nitro-L-arginine methyl ester treatment and fixed-rate atrial pacing showed a trend to suppress the VNS effects, suggesting the involvement of nitric oxide-based signalling and myocardial oxygen consumption. Moreover, VNS decreased the myocardial norepinephrine (NE) level (0.25 +/- 0.07 vs. 0.60 +/- 0.12 ng/mL, P < 0.05; n = 6). Reactive oxygen species production from cultured cardiomyocytes was enhanced by beta-adrenergic activation, which was partially antagonized by 10 micromol/L acetylcholine (ACh) (relative value compared with 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.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takaki
T
Tsutsumi
Tomomi
T
Ide
Mayumi
M
Yamato
Wataru
W
Kudou
Makoto
M
Andou
Yoshitaka
Y
Hirooka
Hideo
H
Utsumi
Hiroyuki
H
Tsutsui
Kenji
K
Sunagawa
D000818:Animals; D002304:Cardiac Pacing, Artificial; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D009638:Norepinephrine