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.
  
  
  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 100μg/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±0.9nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5nmol/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; 10Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6nmol/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.
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center.
authors.forename: Shuji
authors.initials: S
authors.lastname: Shimizu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Michael James
authors.initials: MJ
authors.lastname: Turner
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shishido
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D006321:Heart / Q000294:innervation* / Q000503:physiopathology; D020926:Medetomidine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits; D013270:Stomach / Q000294:innervation* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D014630:Vagus Nerve / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D020926:Medetomidine; D000109:Acetylcholine; D009638:Norepinephrine