title: Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats.
abstract: Desipramine (DMI) is a blocker of neuronal norepinephrine (NE) uptake transporter. Although intravenous DMI has been shown to cause centrally-mediated sympathoinhibition and peripheral NE accumulation, its parasympathetic effect remains to be elucidated. We hypothesized that intravenous DMI activates the cardiac vagal nerve via an α2-adrenergic mechanism. Using a cardiac microdialysis technique, changes in myocardial interstitial acetylcholine (ACh) levels in the left ventricular free wall in response to intravenous DMI (1mg·kg-1) were examined in anesthetized rats. In rats with intact vagi (n=7), intravenous DMI increased ACh from 1.67±0.43 to 2.48±0.66nM (P<0.01). In rats with vagotomy (n=5), DMI did not significantly change ACh (from 0.92±0.16 to 0.85±0.23nM). In rats with intact vagi pretreated with intravenous yohimbine (2mg·kg-1), DMI did not significantly change ACh (from 1.25±0.23 to 1.13±0.15nM). In conclusion, while DMI is generally considered to be an agent that predominantly affects sympathetic neurotransmission, it can activate the cardiac vagal nerve via α2-adrenergic stimulation in experimental settings in vivo.
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Japan. Electronic address: torukawa@ncvc.go.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukumitsu
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D061605:Administration, Intravenous; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010277:Parasympathomimetics / Q000494:pharmacology*; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D002317:Cardiovascular Agents; D010277:Parasympathomimetics; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000109:Acetylcholine; D003891:Desipramine
keywords: Acetylcholine; Cardiac microdialysis; Desipramine; Rats; Yohimbine