title: Effect of clonidine on cardiac baroreflex delay in humans and rats.
abstract: The delay τ between rising systolic blood pressure (SBP) and baroreflex bradycardia has been found to increase when vagal tone is low. The α(2)-agonist clonidine increases cardiac vagal tone, and this study tested how it affects τ. In eight conscious supine human volunteers clonidine (6 μg/kg po) reduced τ, assessed both by cross correlation baroreflex sensitivity and sequence methods (both P < 0.05). Experiments on urethane-anaesthetized rats reproduced the phenomenon and investigated the underlying mechanism. Heart rate (HR) responses to increasing SBP produced with an arterial balloon catheter showed reduced τ (P < 0.05) after clonidine (100 μg/kg iv). The central latency of the reflex was unaltered, however, as shown by the unchanged timing with which antidromically identified cardiac vagal motoneurons (CVM) responded to the arterial pulse. Testing the latency of the HR response to brief electrical stimuli to the right vagus showed that this was also unchanged by clonidine. Nevertheless, vagal stimuli delivered at a fixed time in the cardiac cycle (triggered from the ECG R-wave) slowed HR with a 1-beat delay in the baseline state but a 0-beat delay after clonidine (n = 5, P < 0.05). This was because clonidine lengthened the diastolic period, allowing the vagal volleys to arrive at the heart just in time to postpone the next beat. Calculations indicate that naturally generated CVM volleys in both humans and rats arrive around this critical time. Clonidine thus reduces τ not by changing central or efferent latencies but simply by slowing the heart.
authors.affiliation: Physiology, CNRS-University of Lyon, Lyon, France.
authors.forename: Andrei
authors.initials: A
authors.lastname: Cividjian
authors.forename: Emil
authors.initials: E
authors.lastname: Toader
authors.forename: Karel H
authors.initials: KH
authors.lastname: Wesseling
authors.forename: John M
authors.initials: JM
authors.lastname: Karemaker
authors.forename: Robin
authors.initials: R
authors.lastname: McAllen
authors.forename: Luc
authors.initials: L
authors.lastname: Quintin
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003000:Clonidine