Central actions of agmatine in conscious spontaneously hypertensive rats.
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.
Briaud
S
S
Institut de Recherche Neurologique et Cardiovasculaire, Faculté de Pharmacie de Tours, Tours, France.
Zhang
B L
BL
Sannajust
F
F
D000376:Agmatine / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009068:Movement / Q000187:drug effects; D010080:Oxazoles / Q000008:administration & dosage; D051381:Rats; D011918:Rats, Inbred SHR; D000077769:Rilmenidine
D000959:Antihypertensive Agents; D010080:Oxazoles; D000376:Agmatine; D003000:Clonidine; D000077769:Rilmenidine