title: Centrally administered ghrelin activates cardiac vagal nerve in anesthetized rabbits.
abstract: Although central ghrelin has cardioprotective effect through inhibiting sympathetic nerve activity, the effects of central ghrelin on cardiac vagal nerve remain unknown. We investigated the effects of centrally administered ghrelin on cardiac autonomic nerve activities using microdialysis technique. A microdialysis probe was implanted in the right atrial wall adjacent to the sinoatrial node of an anesthetized rabbit and was perfused with Ringer's solution containing a cholinesterase inhibitor, eserine. After injection of ghrelin (1 nmol) into the right lateral cerebral ventricle, norepinephrine (NE) and acetylcholine (ACh) concentrations in the dialysate samples were measured as indices of NE and ACh release from nerve endings to the sinoatrial node using high-performance liquid chromatography. Heart rate was 270±4 bpm at baseline and decreased gradually after ghrelin injection to 234±9 bpm (P<0.01) at 60-80 min, followed by gradual recovery. Dialysate ACh concentration was 5.5±0.8 nM at baseline and increased gradually after ghrelin injection to 8.8±1.2 nM (P<0.01) at 60-80 min; the concentration started to decrease gradually from 100 to 120 min after injection reaching 5.6±0.8 nM at 160-180 min. Central ghrelin did not change mean arterial pressure or dialysate NE concentration. The elevated dialysate ACh concentration declined rapidly after transection of cervical vagal nerves. These results indicate that centrally administered ghrelin activates cardiac vagal nerve.
authors.affiliation: National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. shujismz@ri.ncvc.go.jp
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: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shishido
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
chemical_list: D054439:Ghrelin; D000109:Acetylcholine; D009638:Norepinephrine