title: Central vagal activation by alpha(2) -adrenergic stimulation is impaired in spontaneously hypertensive rats.
abstract: OBJECTIVE
  To elucidate the abnormality of vagal control in spontaneously hypertensive rats (SHR) by measuring left ventricular myocardial interstitial acetylcholine (ACh) release in response to α(2) -adrenergic stimulation as an index of in vivo vagal nerve activity.
  
  
  METHODS
  A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α(2) -adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats (WKY) and SHR under anaesthetized conditions.
  
  
  RESULTS
  Intravenous medetomidine (0.1 mg kg(-1) ) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L(-1) , P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L(-1) , n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L(-1) , P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L(-1) , P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg(-1) ) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR.
  
  
  CONCLUSIONS
  Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR.
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. torukawa@ri.ncvc.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Kawada
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Kamiya
authors.forename: K
authors.initials: K
authors.lastname: Uemura
authors.forename: Y
authors.initials: Y
authors.lastname: Sata
authors.forename: M
authors.initials: M
authors.lastname: Shirai
authors.forename: M
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D020926:Medetomidine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018341:Receptors, Adrenergic, alpha-2; D020926:Medetomidine; D000109:Acetylcholine