Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction

Takaki Tsutsumi, Tomomi Ide, Mayumi Yamato, Wataru Kudou, Makoto Andou, Yoshitaka Hirooka, Hideo Utsumi, Hiroyuki Tsutsui, Kenji Sunagawa

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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 remodelling, we hypothesized that VNS may modulate the myocardial redox state. Methods and 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. Nω-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 β-adrenergic activation, which was partially antagonized by 10 μmol/L acetylcholine (ACh) (relative value compared with control: NE 3.7 ± 0.5, NE + ACh 2.5 ± 0.3, P < 0.05; n = 12). Conclusion: The present study suggests that VNS modulates the cardiac redox status and adrenergic drive, and thereby suppresses free radical generation in the failing heart.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalCardiovascular research
Volume77
Issue number4
DOIs
Publication statusPublished - Mar 1 2008

Fingerprint

Vagus Nerve Stimulation
Oxidation-Reduction
Myocardial Infarction
Norepinephrine
Heart Failure
Adrenergic Agents
Acetylcholine
Electron Spin Resonance Spectroscopy
Muscarinic Receptors
Atropine
Cardiac Myocytes
Oxygen Consumption
Free Radicals
Reactive Oxygen Species
Nitric Oxide

All Science Journal Classification (ASJC) codes

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

Cite this

Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction. / Tsutsumi, Takaki; Ide, Tomomi; Yamato, Mayumi; Kudou, Wataru; Andou, Makoto; Hirooka, Yoshitaka; Utsumi, Hideo; Tsutsui, Hiroyuki; Sunagawa, Kenji.

In: Cardiovascular research, Vol. 77, No. 4, 01.03.2008, p. 713-721.

Research output: Contribution to journalArticle

Tsutsumi, Takaki ; Ide, Tomomi ; Yamato, Mayumi ; Kudou, Wataru ; Andou, Makoto ; Hirooka, Yoshitaka ; Utsumi, Hideo ; Tsutsui, Hiroyuki ; Sunagawa, Kenji. / Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction. In: Cardiovascular research. 2008 ; Vol. 77, No. 4. pp. 713-721.
@article{3c2596c4e2e248c58bde526bd64503d6,
title = "Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction",
abstract = "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 remodelling, we hypothesized that VNS may modulate the myocardial redox state. Methods and 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. Nω-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 β-adrenergic activation, which was partially antagonized by 10 μmol/L acetylcholine (ACh) (relative value compared with control: NE 3.7 ± 0.5, NE + ACh 2.5 ± 0.3, P < 0.05; n = 12). Conclusion: The present study suggests that VNS modulates the cardiac redox status and adrenergic drive, and thereby suppresses free radical generation in the failing heart.",
author = "Takaki Tsutsumi and Tomomi Ide and Mayumi Yamato and Wataru Kudou and Makoto Andou and Yoshitaka Hirooka and Hideo Utsumi and Hiroyuki Tsutsui and Kenji Sunagawa",
year = "2008",
month = "3",
day = "1",
doi = "10.1093/cvr/cvm092",
language = "English",
volume = "77",
pages = "713--721",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction

AU - Tsutsumi, Takaki

AU - Ide, Tomomi

AU - Yamato, Mayumi

AU - Kudou, Wataru

AU - Andou, Makoto

AU - Hirooka, Yoshitaka

AU - Utsumi, Hideo

AU - Tsutsui, Hiroyuki

AU - Sunagawa, Kenji

PY - 2008/3/1

Y1 - 2008/3/1

N2 - 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 remodelling, we hypothesized that VNS may modulate the myocardial redox state. Methods and 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. Nω-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 β-adrenergic activation, which was partially antagonized by 10 μmol/L acetylcholine (ACh) (relative value compared with control: NE 3.7 ± 0.5, NE + ACh 2.5 ± 0.3, P < 0.05; n = 12). Conclusion: The present study suggests that VNS modulates the cardiac redox status and adrenergic drive, and thereby suppresses free radical generation in the failing heart.

AB - 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 remodelling, we hypothesized that VNS may modulate the myocardial redox state. Methods and 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. Nω-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 β-adrenergic activation, which was partially antagonized by 10 μmol/L acetylcholine (ACh) (relative value compared with control: NE 3.7 ± 0.5, NE + ACh 2.5 ± 0.3, P < 0.05; n = 12). Conclusion: The present study suggests that VNS modulates the cardiac redox status and adrenergic drive, and thereby suppresses free radical generation in the failing heart.

UR - http://www.scopus.com/inward/record.url?scp=39749170512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749170512&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvm092

DO - 10.1093/cvr/cvm092

M3 - Article

VL - 77

SP - 713

EP - 721

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 4

ER -