Cardioinhibitory actions of clonidine assessed by cardiac vagal motoneuron recordings

Abstract

Cardiac vagal activity is now considered as an important therapeutic target. However, there is a lack of direct data on how cardiac vagal motoneurons respond to parasympathomimetic agents. Rats were anesthetized with urethane and mechanically ventilated. Single-unit activity was recorded in the nucleus ambiguus from cardiac vagal motoneurons, identified by antidromic activation from the cardiac vagal branch and their barosensitivity. Nitroprusside lowered systolic blood pressure, increased heart rate and inhibited cardiac vagal motoneuron activity (n = 5 cells in five rats). Clonidine 1-100 microg kg(-1) intravenously, however, lowered systolic blood pressure, but it increased cardiac vagal motoneuron activity (n = 8 cells in eight rats). It also enhanced their barosensitivity. An unsuspected further finding was that clonidine significantly increased the occurrence of cardiac vagal motoneuron firing spikes separated by short (< 30 ms) interspike intervals ('doublet'). Such grouped patterns are known to enhance neurotransmitter release. Therefore, these data provide a new mechanism by which clonidine can further potentiate parasympathetic actions on the heart.