Document Detail

Central actions of agmatine in conscious spontaneously hypertensive rats.
MedLine Citation:
PMID:  16303638     Owner:  NLM     Status:  MEDLINE    
Agmatine (decarboxylated arginine) is an endogenous ligand at alpha-2 adrenergic and imidazoline nonadrenergic receptors. In conscious spontaneously hypertensive rats (SHRs), we have studied its central effects on cardiovascular function and its interaction with the second generation centrally acting antihypertensive agent, rilmenidine, and the reference imidazoline, clonidine, which are mixed alpha-2 adrenoceptor/imidazoline receptor agonists. Agmatine, when administered in low doses (30-100 microg/kg) into the fourth ventricle had no effect on blood pressure and caused an increase in heart rate. A higher dose of 1,000 microg/kg produced an adverse reaction in conscious SHRs and a marked and long-lasting increase in blood pressure. The effects of fourth ventricular rilmenidine (300 microg/kg) and clonidine (10 microg/kg) were equihypotensive and equibradycardic. The antihypertensive and bradycardic effects of rilmenidine were not reversed by cumulative intracisternal doses (30-100-300 microg/kg) of agmatine. The bradycardia obtained 20 min after intracisternal administration of clonidine in the fourth ventricle was reversed by 30 microg/kg agmatine. Only the highest dose of agmatine (1,000 microg/kg) did reverse the antihypertensive effects of rilmenidine and clonidine. Agmatine neither did mimic nor block the antihypertensive response to rilmenidine and clonidine at well-tolerated doses. Yet agmatine produced a small tachycardia at relatively low doses and was able to reverse the bradycardia induced by clonidine. Therefore, its affinity for alpha-2 adrenoceptors in vitro might partially explain its cardiovascular effects in vivo.
S Briaud; B L Zhang; F Sannajust
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental hypertension (New York, N.Y. : 1993)     Volume:  27     ISSN:  1064-1963     ISO Abbreviation:  Clin. Exp. Hypertens.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-23     Completed Date:  2006-02-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9305929     Medline TA:  Clin Exp Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  619-27     Citation Subset:  IM    
Institut de Recherche Neurologique et Cardiovasculaire, Faculté de Pharmacie de Tours, Tours, France.
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MeSH Terms
Agmatine / administration & dosage*
Antihypertensive Agents / administration & dosage
Blood Pressure / drug effects
Brain / drug effects*
Cardiovascular System / drug effects*
Clonidine / administration & dosage
Dose-Response Relationship, Drug
Drug Interactions
Heart Rate / drug effects
Hypertension / physiopathology
Injections, Intraventricular
Movement / drug effects
Oxazoles / administration & dosage
Rats, Inbred SHR
Reg. No./Substance:
0/Antihypertensive Agents; 0/Oxazoles; 306-60-5/Agmatine; 4205-90-7/Clonidine; 54187-04-1/rilmenidine

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