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.