title: Pharmacological evidence that alpha2A- and alpha2C-adrenoceptors mediate the inhibition of cardioaccelerator sympathetic outflow in pithed rats.
abstract: It has been suggested that the alpha(2)-adrenoceptors mediating cardiac sympatho-inhibition in pithed rats closely resemble the pharmacological profile of the alpha(2A)-adrenoceptor subtype. However, several lines of evidence suggest that more than one subtype may be involved. Thus, the present study has pharmacologically re-evaluated the receptor subtype(s) involved in the inhibitory effect of the alpha(2)-adrenoceptor agonist, B-HT 933, on the tachycardic responses elicited by selective cardiac sympathetic stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) in desipramine-pretreated pithed rats. I.v. continuous infusions of B-HT 933 (30 microg/kg min), which failed to modify the tachycardic responses to exogenous noradrenaline, inhibited those induced by preganglionic (C(7)-T(1)) stimulation of the cardiac sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). This cardiac sympatho-inhibitory response to B-HT 933 was: (1) unaltered by saline (1 ml/kg) or the antagonists BRL44408 (100 microg/kg; alpha(2A)) or imiloxan (3000 and 10,000 microg/kg; alpha(2B)); (2) partially antagonized by BRL44408 (300 microg/kg) or MK912 (10 microg/kg; alpha(2C)) given separately; and (3) completely antagonized by rauwolscine (300 microg/kg; alpha(2)), MK912 (30 microg/kg) or the combination of BRL44408 (300 microg/kg) plus MK912 (10 microg/kg). Moreover, the above doses of antagonists, which are high enough to block their respective receptors, failed to block per se the tachycardic responses to sympathetic stimulation. These results suggest that the cardiac sympatho-inhibition induced by B-HT 933 in pithed rats is mainly mediated by stimulation of alpha(2A)- and alpha(2C)-adrenoceptors.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., México.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Cobos-Puc
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez-López
authors.forename: Jair
authors.initials: J
authors.lastname: Lozano-Cuenca
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Pertz
authors.forename: Tilo
authors.initials: T
authors.lastname: Görnemann
authors.forename: David
authors.initials: D
authors.lastname: Centurión
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D054833:Isoindoles; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013610:Tachycardia / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D011807:Quinolizines; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; C015603:azepexole; D009638:Norepinephrine; C072125:BRL 44408; C044484:Imiloxan