title: The α2-adrenoceptors mediating inhibition of the vasopressor sympathetic outflow in pithed rats: pharmacological correlation with α2A, α2B and α2C subtypes.
abstract: α2-Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In vitro studies have confirmed that α2A, α2B and α2C subtypes inhibited noradrenaline release from postganglionic sympathetic neurons but no study has been reported their involvement in the vasopressor sympathetic outflow in vivo. Thus, this study analysed the subtype(s) involved in the inhibition produced by the α2-adrenoceptor agonist, B-HT 933, on the vasopressor sympathetic outflow. Male Wistar pithed rats were pre-treated with i.v. bolus injections of gallamine (25mg/kg) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9) or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or exogenous noradrenaline produced, respectively, frequency-dependent and dose-dependent vasopressor responses. I.v. continuous infusion of B-HT 933 (30 μg/kg min) failed to modify the vasopressor responses to exogenous noradrenaline and inhibited those induced by preganglionic stimulation of the vasopressor sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii) partially antagonised by BRL44408 (300 μg/kg; α2A), imiloxan (3000 μg/kg; α2B) and/or JP-1302 (300 μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300 μg/kg) or the combination of BRL44408 (300 μg/kg)+imiloxan (3000 μg/kg)+JP-1302 (300 μg/kg). The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. These results suggest that the vasopressor sympatho-inhibition to B-HT 933 is primarily mediated by activation of α2A/2B/2C-adrenoceptors in pithed rats.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico.
authors.forename: Ma Trinidad
authors.initials: MT
authors.lastname: Villamil-Hernández
authors.forename: Oscar
authors.initials: O
authors.lastname: Alcántara-Vázquez
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez-López
authors.forename: David
authors.initials: D
authors.lastname: Centurión
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D001381:Azepines; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; C015603:azepexole; D009638:Norepinephrine
keywords: B-HT 933; BRL44408; Imiloxan; JP-1302; Sympatho-inhibition; α(2)-Adrenoceptors