Pharmacological characterization of ergotamine-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats.
Ergotamine inhibits the sympathetically-induced tachycardia in pithed rats. The present study identified the pharmacological profile of this response. Male Wistar rats were pithed and prepared to stimulate the preganglionic (C(7)-T(1)) cardiac sympathetic outflow. Intravenous continuous infusions of ergotamine dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. Using several antagonists, the sympatho-inhibition to ergotamine was: (1) partially blocked by rauwolscine (alpha(2)), haloperidol (D(1/2)-like) or rauwolscine plus GR127935 (5-HT(1B/1D)); (2) abolished by rauwolscine plus haloperidol; and (3) unaffected by either saline or GR127935. In animals systematically pretreated with haloperidol, this sympatho-inhibition was: (1) unaffected by BRL44408 (alpha(2A)), partially antagonized by MK912 (alpha(2C)); and (3) abolished by BRL44408 plus MK912. These antagonists failed to modify the sympathetically induced tachycardic responses per se. Thus, the cardiac sympatho-inhibition by ergotamine may be mainly mediated by alpha(2A)/alpha(2C)-adrenoceptors, D(2)-like receptors and, to a lesser extent, by 5-HT(1B/1D) receptors.
Cobos-Puc
Luis E
LE
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., México.
Villalón
Carlos M
CM
Sánchez-López
Araceli
A
Ramírez-Rosas
Martha B
MB
Lozano-Cuenca
Jair
J
Pertz
Heinz H
HH
Görnemann
Tilo
T
Centurión
David
D
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004878:Ergotamine / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013610:Tachycardia / Q000503:physiopathology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D065127:Dopamine D2 Receptor Antagonists; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D018341:Receptors, Adrenergic, alpha-2; D017448:Receptors, Dopamine D2; D004878:Ergotamine
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