Pharmacological characterization of the inhibition by moxonidine and agmatine on the cardioaccelerator sympathetic outflow in pithed rats
This study analysed the inhibition produced by the agonists moxonidine (imidazoline I1receptors > α2-adrenoceptors) and agmatine (endogenous ligand of imidazoline I1/I2receptors), using B-HT 933 (6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepin-2-amine dihydrochloride; α2-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 I1receptors] or BU224 (2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride; 300 μg/kg; imidazoline I2receptors) and abolished by rauwolscine (300 μg/kg; α2-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 α2-adrenoceptors; and (2) 10 μg/kg min moxonidine or 1000 μg/kg min agmatine involves α2-adrenoceptors and imidazoline I1receptors.
|Keywords||-adrenoceptor, 2, AGN192403, BU224, Imidazoline receptors, Moxonidine, Sympatho-inhibition, α|
|Persistent URL||dx.doi.org/10.1016/j.ejphar.2009.06.003, hdl.handle.net/1765/24352|
Cobos-Puc, L.E., Villalón, C.M., Ramírez-Rosas, M.B., Sánchez-López, A., Lozano-Cuenca, J., Gómez-Díaz, B., … Centurion, D.. (2009). Pharmacological characterization of the inhibition by moxonidine and agmatine on the cardioaccelerator sympathetic outflow in pithed rats. European Journal of Pharmacology, 616(1-3), 175–182. doi:10.1016/j.ejphar.2009.06.003