Document Detail


Effect of clonidine on cardiac norepinephrine spillover in isolated rat heart.
MedLine Citation:
PMID:  15167277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study is to determine the effect of clonidine on cardiac norepinephrine spillover utilizing an isolated rat heart preparation with attached cardiac sympathetic nerves. Following a 20-minute stabilization period, the sympathetic ganglion for each heart preparation was electrically stimulated with 10V and 2 Hz for 30 seconds (S1: 60 pulses). Heart rate, left ventricular developed pressure, and coronary perfusion pressure was allowed to return to baseline and the perfusate was randomly switched to Krebs buffer containing one of two treatments: placebo or clonidine (1 microM). After 10 minutes of treatment, the sympathetic ganglion was again electrically stimulated with 10V and 2 Hz for 30 seconds (S2: 60 pulses). The perfusate exiting the heart before, during, and after each electrical stimulation was collected for the determination of cardiac norepinephrine spillover. Clonidine administration significantly reduced cardiac norepinephrine spillover by approximately 50% (P < 0.05) and was associated with a 36% reduction in heart rate (P < 0.05). These findings provide evidence that clonidine can directly suppress NE spillover from cardiac sympathetic nerve terminals. Thus, suppression of cardiac NE by clonidine may be due to stimulation of presynaptic alpha2-adrenergic receptors or imidazoline subtype I receptors located on cardiac sympathetic nerve terminals. Results from our study demonstrate a reduction in cardiac NE spillover by clonidine and provide additional evidence that it can directly suppress peripheral sympathetic activity in that our results were obtained utilizing an isolated perfused heart preparation with attached cardiac sympathetic nerves devoid of any CNS input.
Authors:
Wendell S Akers; Shilpa K Shah; Jeremy D Flynn; Subbu Apparsundaram
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  43     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-05-28     Completed Date:  2004-09-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  830-8     Citation Subset:  IM    
Affiliation:
University of Kentucky College of Pharmacy, Division of Pharmacy Practice & Science, Lexington 40536-0082, USA. wcaker0@uky.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Clonidine / pharmacology*
Electric Stimulation / methods
Heart / drug effects*,  innervation,  physiopathology*
Heart Rate / drug effects
Male
Myocardium / metabolism
Norepinephrine / metabolism*,  physiology
Perfusion
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
4205-90-7/Clonidine; 51-41-2/Norepinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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