Pharmacological characterization of the inhibition by moxonidine and agmatine on the cardioaccelerator sympathetic outflow in pithed rats

• Published in: European journal of pharmacology Vol. 616; no. 1; pp. 175 - 182
• Main Authors: Cobos-Puc, Luis E., Villalón, Carlos M., Ramírez-Rosas, Martha B., Sánchez-López, Araceli, Lozano-Cuenca, Jair, Gómez-Díaz, Benjamín, MaassenVanDenBrink, Antoinette, Centurión, David
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-08-2009; Elsevier
• Subjects: Adrenergic alpha-2 Receptor Agonists; Agmatine - pharmacology; AGN192403; Animals; Azepines - pharmacology; Biological and medical sciences; Brain - surgery; Bridged Bicyclo Compounds - administration & dosage; Bridged Bicyclo Compounds - pharmacology; BU224; Electric Stimulation; Heart Rate - drug effects; Heptanes - administration & dosage; Heptanes - pharmacology; Imidazoles - administration & dosage; Imidazoles - pharmacology; Imidazoline receptors; Infusions, Intravenous; Male; Medical sciences; Moxonidine; Norepinephrine - administration & dosage; Norepinephrine - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Sodium Chloride - administration & dosage; Sodium Chloride - pharmacology; Substrate Specificity; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Sympathetic Nervous System - physiopathology; Sympatho-inhibition; Tachycardia - physiopathology; Time Factors; Yohimbine - administration & dosage; Yohimbine - pharmacology; α 2-adrenoceptor; BU224; Imidazoline receptors; AGN192403; Sympatho-inhibition; α 2-adrenoceptor; Moxonidine; α2-Adrenergic receptor; Imidazole derivatives; Agonist; adrenoceptor; Rat; Rodentia; Imidazoline derivatives; Sympathetic nervous system; Characterization; Imidazoline receptor; α; Vertebrata; Mammalia; Autonomic nervous system; Animal; Antihypertensive agent; α-Adrenergic receptor agonist; Agmatine
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.06.003

This study analysed the inhibition produced by the agonists moxonidine (imidazoline I
1 receptors
>
α
2-adrenoceptors) and agmatine (endogenous ligand of imidazoline I
1/I
2 receptors), using B-HT 933 (6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepin-2-amine dihydrochloride; α
2-adrenoceptors) for comparison, on the rat cardioaccelerator sympathetic outflow. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or noradrenaline produced, respectively, frequency-dependent and dose-dependent tachycardic responses. I.v. continuous infusions of moxonidine (3 and 10
µg/kg min), agmatine (1000 and 3000
µg/kg min) and B-HT 933 (30 and 100
µg/kg min) inhibited the tachycardic responses to sympathetic stimulation, but not those to noradrenaline. The cardiac sympatho-inhibition by either moxonidine (3
µg/kg min) or B-HT 933 (30
µg/kg min) was not modified by i.v. injections of saline or the antagonists AGN192403 [(±)-2-endo-Amino-3-exo-isopropylbicyclo[2.2.1]heptane hydrochloride; 3000
µg/kg; imidazoline I
1 receptors] or BU224 (2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride; 300
µg/kg; imidazoline I
2 receptors) and abolished by rauwolscine (300
µg/kg; α
2-adrenoceptors). At the same doses of these compounds, the sympatho-inhibition to moxonidine (10
µg/kg min) and agmatine (1000
µg/kg min) was: (1) not modified by saline, AGN192403 or BU224; (2) partially blocked by rauwolscine or the combination of rauwolscine plus BU224; and (3) abolished by the combination of rauwolscine plus AGN192403. These results demonstrate that the cardiac sympatho-inhibition to: (1) 3
µg/kg min moxonidine or 30
µg/kg min B-HT 933 involves α
2-adrenoceptors; and (2) 10
µg/kg min moxonidine or 1000
µg/kg min agmatine involves α
2-adrenoceptors and imidazoline I
1 receptors.