Medetomidine, an α2-adrenergic agonist, activates cardiac vagal nerve through modulation of baroreflex control

Shuji Shimizu, Tsuyoshi Akiyama, Toru Kawada, Yusuke Sata, Masaki Mizuno, Atsunori Kamiya, Toshiaki Shishido, Masashi Inagaki, Mikiyasu Shirai, Shunji Sano, Masaru Sugimachi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Although α2-adrenergic agonists have been reported to induce a vagal-dominant condition through suppression of sympathetic nerve activity, there is little direct evidence that they directly increase cardiac vagal nerve activity. Using a cardiac microdialysis technique, we investigated the effects of medetomidine, an α2-adrenergic agonist, on norepinephrine (NE) and acetylcholine (ACh) release from cardiac nerve endings. Methods and Results: A microdialysis probe was implanted into the right atrial wall near the sinoatrial node in anesthetized rabbits and perfused with Ringer's solution containing eserine. Dialysate NE and ACh concentrations were measured using high-performance liquid chromatography. Both 10 and 100 μg/kg of intravenous medetomidine significantly decreased mean blood pressure (BP) and the dialysate NE concentration, but only 100 μg/kg of medetomidine enhanced ACh release. Combined administration of medetomidine and phenylephrine maintained mean BP at baseline level, and augmented the medetomidine-induced ACh release. When we varied the mean BP using intravenous administration of phenylephrine, treatment with medetomidine significantly steepened the slope of the regression line between mean BP and log ACh concentration. Conclusions: Medetomidine increased ACh release from cardiac vagal nerve endings and augmented baroreflex control of vagal nerve activity.

Original languageEnglish
Pages (from-to)152-159
Number of pages8
JournalCirculation Journal
Volume76
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Acetylcholine
  • Norepinephrine
  • Sinoatrial node
  • Sympathetic nervous system
  • Vagus nerve

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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