title: Medetomidine, an α(2)-adrenergic agonist, activates cardiac vagal nerve through modulation of baroreflex control.
abstract: BACKGROUND
  Although α(2)-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 α(2)-adrenergic agonist, on norepinephrine (NE) and acetylcholine (ACh) release from cardiac nerve endings.
  
  
  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 100µg/kg of intravenous medetomidine significantly decreased mean blood pressure (BP) and the dialysate NE concentration, but only 100µg/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.
authors: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan. shujismz@ri.ncvc.go.jp
authors: Shuji
authors: S
authors: Shimizu
authors: Tsuyoshi
authors: T
authors: Akiyama
authors: Toru
authors: T
authors: Kawada
authors: Yusuke
authors: Y
authors: Sata
authors: Masaki
authors: M
authors: Mizuno
authors: Atsunori
authors: A
authors: Kamiya
authors: Toshiaki
authors: T
authors: Shishido
authors: Masashi
authors: M
authors: Inagaki
authors: Mikiyasu
authors: M
authors: Shirai
authors: Shunji
authors: S
authors: Sano
authors: Masaru
authors: M
authors: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000294:innervation*; D020926:Medetomidine / Q000494:pharmacology*; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods; D023421:Models, Animal; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D010656:Phenylephrine; D020926:Medetomidine; D000109:Acetylcholine; D009638:Norepinephrine