title: Pharmacological analysis of the cardiac sympatho-inhibitory actions of moxonidine and agmatine in pithed spontaneously hypertensive rats.
abstract: This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine. In SHR, 300μg/kg rauwolscine failed to block the sympatho-inhibition to 100μg/kgmin B-HT 933 or 10μg/kgmin moxonidine, but 1000μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000μg/kg AGN 192403 or 300μg/kg BU224 given alone had no effect in the moxonidine- or agmatine-induced sympatho-inhibition, and the combination rauwolscine plus AGN 192403 but not plus BU224, abolished the sympatho-inhibition to the highest doses of moxonidine and agmatine. In conclusion, the sympathetically-induced tachycardic responses in SHR are inhibited by moxonidine and agmatine. The inhibition of moxonidine is mainly mediated by prejunctional α2-adrenoceptors and to a lesser extent by I1-imidazoline receptors, while the inhibition of agmatine is mediated by prejunctional α2-adrenoceptors and I1-imidazoline receptors at the same extent. Notwithstanding, the inhibitory function of α2-adrenoceptors seems to be altered in SHR compared with Wistar normotensive rats.
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 Ciudad de México, Mexico; Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard Venustiano Carranza esquina con Ing. José Cárdenas Valdés, Colonia República, Saltillo, C.P. 25280 Coahuila, Mexico.
authors: Luis E
authors: LE
authors: Cobos-Puc
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 Ciudad de México, Mexico.
authors: Araceli
authors: A
authors: Sánchez-López
authors: Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard Venustiano Carranza esquina con Ing. José Cárdenas Valdés, Colonia República, Saltillo, C.P. 25280 Coahuila, Mexico. Electronic address: dcenturi@cinvestav.mx.
authors: David
authors: D
authors: Centurión
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006536:Heptanes / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C098523:AGN 192403; C105826:BU 224; D001643:Bridged Bicyclo Compounds; D006536:Heptanes; D007093:Imidazoles; D015016:Yohimbine; D000376:Agmatine; C043482:moxonidine; D009638:Norepinephrine
keywords: (±)-noradrenaline bitartrate salt (PubChem CID: 5813); AGN 192403 hydrochloride (PubChem CID: 11957452); Agmatine; Agmatine sulfate salt (PubChem CID: 2794990); B-HT 933 dihydrochloride (PubChem CID: 169743); BU224 hydrochloride (PubChem CID: 11957470); Hypertension; I(1)-imidazoline receptor; Moxonidine; desipramine hydrochloride (PubChem CID: 65327); gallamine triethiodide (PubChem CID: 6172); moxonidine hydrochloride (PubChem CID: 11231255); rauwolscine hydrochloride (PubChem CID: 197067); α(2)-adrenoceptor