Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve

Shuji Shimizu, Tsuyoshi Akiyama, Toru Kawada, Atsunori Kamiya, Michael James Turner, Hiromi Yamamoto, Toshiaki Shishido, Mikiyasu Shirai, Masaru Sugimachi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100 μg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9 nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5 nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10 Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8 nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6 nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.

Original languageEnglish
Pages (from-to)1405-1413
Number of pages9
JournalCirculation Journal
Volume78
Issue number6
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Medetomidine
Vagus Nerve
Stomach
Acetylcholine
Norepinephrine
Heart Failure
Pharmacology
Vagus Nerve Stimulation
Autonomic Pathways
Dialysis Solutions
Microdialysis
High Pressure Liquid Chromatography
Rabbits

Keywords

  • Acetylcholine
  • Norepinephrine
  • Sympathetic nerve activity
  • Vagus nerve activity
  • α2-adrenergic agonist

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve. / Shimizu, Shuji; Akiyama, Tsuyoshi; Kawada, Toru; Kamiya, Atsunori; Turner, Michael James; Yamamoto, Hiromi; Shishido, Toshiaki; Shirai, Mikiyasu; Sugimachi, Masaru.

In: Circulation Journal, Vol. 78, No. 6, 01.01.2014, p. 1405-1413.

Research output: Contribution to journalArticle

Shimizu, S, Akiyama, T, Kawada, T, Kamiya, A, Turner, MJ, Yamamoto, H, Shishido, T, Shirai, M & Sugimachi, M 2014, 'Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve', Circulation Journal, vol. 78, no. 6, pp. 1405-1413. https://doi.org/10.1253/circj.CJ-13-1456
Shimizu, Shuji ; Akiyama, Tsuyoshi ; Kawada, Toru ; Kamiya, Atsunori ; Turner, Michael James ; Yamamoto, Hiromi ; Shishido, Toshiaki ; Shirai, Mikiyasu ; Sugimachi, Masaru. / Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve. In: Circulation Journal. 2014 ; Vol. 78, No. 6. pp. 1405-1413.
@article{eef2719492174e2eb2c7cc1947cbc1d9,
title = "Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve",
abstract = "Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100 μg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9 nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5 nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10 Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8 nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6 nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.",
keywords = "Acetylcholine, Norepinephrine, Sympathetic nerve activity, Vagus nerve activity, α2-adrenergic agonist",
author = "Shuji Shimizu and Tsuyoshi Akiyama and Toru Kawada and Atsunori Kamiya and Turner, {Michael James} and Hiromi Yamamoto and Toshiaki Shishido and Mikiyasu Shirai and Masaru Sugimachi",
year = "2014",
month = "1",
day = "1",
doi = "10.1253/circj.CJ-13-1456",
language = "English",
volume = "78",
pages = "1405--1413",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "6",

}

TY - JOUR

T1 - Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve

AU - Shimizu, Shuji

AU - Akiyama, Tsuyoshi

AU - Kawada, Toru

AU - Kamiya, Atsunori

AU - Turner, Michael James

AU - Yamamoto, Hiromi

AU - Shishido, Toshiaki

AU - Shirai, Mikiyasu

AU - Sugimachi, Masaru

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100 μg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9 nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5 nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10 Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8 nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6 nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.

AB - Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100 μg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9 nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5 nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10 Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8 nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6 nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.

KW - Acetylcholine

KW - Norepinephrine

KW - Sympathetic nerve activity

KW - Vagus nerve activity

KW - α2-adrenergic agonist

UR - http://www.scopus.com/inward/record.url?scp=84901305895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901305895&partnerID=8YFLogxK

U2 - 10.1253/circj.CJ-13-1456

DO - 10.1253/circj.CJ-13-1456

M3 - Article

C2 - 24727611

AN - SCOPUS:84901305895

VL - 78

SP - 1405

EP - 1413

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 6

ER -