TY - JOUR
T1 - Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats
AU - Kawada, Toru
AU - Akiyama, Tsuyoshi
AU - Shimizu, Shuji
AU - Fukumitsu, Masafumi
AU - Kamiya, Atsunori
AU - Sugimachi, Masaru
N1 - Funding Information:
This study was partly supported by a Grant-in-Aid for Scientific Research (JSPS KAKENHI grants 26462774, 15K09110, 15H03101) and the Takeda Medical Research Foundation. The authors confirm that the funders had no influence over the study design, contents of the article, or selection of this journal.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/7
Y1 - 2017/7
N2 - 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 (1 mg·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 ± 0.66 nM (P < 0.01). In rats with vagotomy (n = 5), DMI did not significantly change ACh (from 0.92 ± 0.16 to 0.85 ± 0.23 nM). In rats with intact vagi pretreated with intravenous yohimbine (2 mg·kg− 1), DMI did not significantly change ACh (from 1.25 ± 0.23 to 1.13 ± 0.15 nM). 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.
AB - 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 (1 mg·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 ± 0.66 nM (P < 0.01). In rats with vagotomy (n = 5), DMI did not significantly change ACh (from 0.92 ± 0.16 to 0.85 ± 0.23 nM). In rats with intact vagi pretreated with intravenous yohimbine (2 mg·kg− 1), DMI did not significantly change ACh (from 1.25 ± 0.23 to 1.13 ± 0.15 nM). 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.
KW - Acetylcholine
KW - Cardiac microdialysis
KW - Desipramine
KW - Rats
KW - Yohimbine
UR - http://www.scopus.com/inward/record.url?scp=85013627557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85013627557&partnerID=8YFLogxK
U2 - 10.1016/j.autneu.2017.02.005
DO - 10.1016/j.autneu.2017.02.005
M3 - Article
C2 - 28242182
AN - SCOPUS:85013627557
VL - 205
SP - 21
EP - 25
JO - Journal of the Autonomic Nervous System
JF - Journal of the Autonomic Nervous System
SN - 1566-0702
ER -